Vein of Galen aneurysmal malformation: does size affect outcome?

PURPOSE: To validate a semiautomated method for segmenting vein of Galen aneurysmal malformations (VGAM) and to assess the relationship between VGAM volume and other angioarchitectural features, cardiological findings, and outcomes. METHODS: In this retrospective study, we selected all subjects with VGAM admitted to the Gaslini Children's Hospital between 2009 and 2022. Clinical data were retrieved from electronic charts. We compared 3D-Slicer segmented VGAM volumes obtained by two independent observers using phase-contrast MR venography to those obtained with manual measurements performed on T2-weighted images. The relationship between VGAM volumes and clinical and neuroimaging features was then explored. RESULTS: Forty-three subjects with VGAM (22 males, mean age 6.56 days) were included in the study. Manual and semiautomated VGAM volumes were well correlated for both readers (r = 0.86 and 0.82, respectively). Regarding reproducibility, the inter-rater interclass correlation coefficients were 0.885 for the manual method and 0.992 for the semiautomated method (p < 0.001). The standard error for repeated measures was lower for the semiautomated method (0.04 versus 0.40 of manual method). Higher VGAM volume was associated with superior sagittal sinus narrowing, jugular bulb stenosis, and aqueductal stenosis (p < 0.05). A weak correlation was found between VGAM volume and straight sinus dilatation (r = 0.331) and superior sagittal sinus index (r = - 0.325). No significant associations were found with cardiac findings, post-embolization complications, and outcome (p > 0.05). CONCLUSIONS: Semiautomated VGAM volumetry is feasible and reliable with improved reproducibility compared to the manual method. VGAM volume is not a prognostic factor for clinical outcome, but it is related to other venous findings with potential hemodynamic effects.

The increase of bronchiolitis severity in the 2022-2023 season in an Italian tertiary children's hospital: An isolated phenomenon or a warning sign?

AIM: Recent literature has shown epidemiological changes in bronchiolitis with an increased incidence in the post-SARS-CoV-2 pandemic period but reports regarding disease severity are conflicting. We aimed to describe the epidemiology, disease severity, and microbiology of bronchiolitis during the 2022-2023 cold season compared to the previous 5 years. METHODS: This single-center retrospective observational study at IRCCS Gaslini, Italy, included all children aged 0-2 years hospitalized for bronchiolitis from 1 September 2017 to 31 August 2023. Findings from the 2022-2023 season were compared to the previous 5 years. RESULTS: We observed a statistically significant increase in the 2022-2023 season in the absolute number of bronchiolitis admissions. Children who required mechanical ventilation (MV) dramatically increased from a total of seven patients in the previous five seasons to 17 in the 2022-2023 season alone (p = .001). All other severity parameters significantly increased: the need for respiratory support (p = .002), the median length of stay (5 days vs. 4 days, p = .001), and the median duration of respiratory support (4 days vs. 3 days, p = .016). CONCLUSIONS: We report a substantial increase in the severity of bronchiolitis in the season 2022-2023 with a remarkable number of previously healthy infants requiring MV. Further studies are needed to confirm whether our findings are an isolated phenomenon or part of a true global trend. Health systems need to be prepared and protective preventive measures should be implemented for all newborns.

Severe Lactic Acidosis Caused by Thiamine Deficiency in a Child with Relapsing Acute Lymphoblastic Leukemia: A Case Report.

Lactic acidosis is characterized by an excessive production of lactic acid or by its impaired clearance. Thiamine deficiency is an uncommon cause of lactic acidosis, especially in countries where malnutrition is rare. We describe the case of a 5-year-old boy who presented with a central nervous system relapse of acute lymphoblastic leukemia. During the chemotherapy regimen, the patient developed drug-induced pancreatitis with paralytic ileus requiring prolonged glucosaline solution infusion. In the following days, severe lactic acidosis (pH 7.0, lactates 253 mg/dL, HCO3- 8 mmol/L) was detected, associated with hypoglycemia (42 mg/dL) and laboratory signs of acute liver injury. Due to the persistent hypoglycemia, the dextrose infusion was gradually increased. Lactates, however, continued to raise, so continuous venovenous hemodiafiltration was started. While lactates initially decreased, 12 h after CVVHDF suspension, they started to raise again. Assuming that it could have been caused by mitochondrial dysfunction due to vitamin deficiency after prolonged fasting and feeding difficulties, parenteral nutrition and thiamine were administered, resulting in a progressive reduction in lactates, with the normalization of pH during the next few hours. In the presence of acute and progressive lactic acidosis in a long-term hospitalized patient, thiamine deficiency should be carefully considered and managed as early as possible.

Vein of Galen aneurysmal malformation in newborns: a retrospective study to describe a paradigm of treatment and identify risk factors of adverse outcome in a referral center.

Background: Vein of Galen aneurysmal malformation (VGAM) is a rare cerebral vascular malformation associated with significant morbidity and mortality. Newborns with VGAM without adequate treatment may develop rapidly deteriorating high output heart failure (HOHF) and are at risk for severe neurological outcomes. Objective: To describe the clinical course and management of newborns with VGAM, and identify which echocardiographic and neuroradiologic factors may be associated with severe heart failure at birth and adverse short term outcomes. Methods: This is a single center retrospective cohort study including all consecutive newborns with VGAM admitted to Gaslini Children's Hospital between 2009 and 2022. We reviewed clinical data, intensive care support, fetal and neonatal cardiologic and neuroradiologic findings and we studied the association with severe HOHF, endovascular complications and death. Results: Out of 40 newborns, 17 (42.5%) developed severe HOHF requiring early endovascular procedures. Medical treatment was focused on the main components of HOHF by providing inotropic support and peripheral vasodilation. Pulmonary vasodilators were avoided to reduce the negative effects of pulmonary overflow and prevent vascular remodeling. Reduction of the obligatory left to right shunt through the VGAM was possible only through endovascular treatment. Fetal cardiothoracic ratio was significantly associated with severe HOHF at birth and death. Cardiologic parameters of right ventricular overload, pulmonary hypertension and systemic steal were the leading findings associated with haemodynamic compromise at birth. The mediolateral diameter of the straight or falcine sinus at its shortest section (SS-MD), and arterial pseudofeeders were significantly associated with severe HOHF at birth in prenatal and postnatal assessments. None of the postnatal echocardiographic and MRI variables, nor a higher inotropic support were associated with major periprocedural complications or death. Mortality was due to palliation for congenital severe brain damage (4/40, 10%), or major periprocedural complications (3/40, 7.5%). None of the patients died due to HOHF and multiorgan failure. Overall survival at discharge was 82.5% (33/40). Conclusions: The complexity of neonatal VGAM pathophysiology requires a multidisciplinary approach, specialized intensive care management, and early endovascular treatment to reduce mortality and optimize clinical outcomes. Cardiologic and neuroradiologic parameters are key to define risk stratification and treatment strategies.

Avaliação da eficácia do acessório mamilo na remoção dos hábitos deletérios / Evaluation of the effectiveness of the nipple accessory in the removal of the deletery habits

Objetivo: avaliar a eficácia do acessório mamilo aplicado a aparelhos ortopédicos/ ortodônticos no tratamento de hábitos deletérios de sucção de chupeta, língua, lábio e dedo, e onicofagia em pacientes tratados nos últimos 20 anos com o aparelho. Métodos: Trata-se de um estudo clínico observacional, retrospectivo, no qual a amostra foi composta de prontuários de pacientes de ambos os gêneros, atendidos por profissionais habilitados pelo aparelho mamilo, que os utilizaram em crianças de 03 a 16 anos portadoras de hábitos deletérios. Os prontuários utilizados, correspondem a pacientes tratados entre os anos 2000 a 2020. Todas as análises foram realizadas no programa R, com nível de significância de 5%. Resultados: Foram analisados 142 prontuários, nos quais 122 foram incluídos, por estarem dentro dos critérios de inclusão propostos no estudo e 20 foram excluídos da pesquisa por apresentarem informações incompletas e/ou não preenchidas corretamente. O hábito com maior incidência foi o de sucção digital, em 71,3% dos pacientes, 91,8% dos pacientes deixaram o hábito, destacando que nos casos de sucção de chupeta e onicofagia, o sucesso na remoção do hábito foi de 100%, em ambos os casos. O tempo médio de uso do aparelho foi de 4,8 meses, variando de 0,6 a 14 meses. O tempo médio para a remoção do hábito após a instalação do aparelho foi de 1,6 meses, variando de 0 a 12 meses. Conclusão: O aparelho mamilo, mostra-se como uma alternativa de alta eficácia na remoção de hábitos deletérios de sução de chupeta, dedo, língua e onicofagia.(AU)

Objective: Evaluate the effectiveness of the nipple accessory applied to orthopedic/orthodontic appliances in the treatment of harmful pacifier, tongue, lip and finger sucking habits, and onychophagia in patients treated in the last 20 years with the device. Methods: This is an observational, retrospective clinical study, in which the sample consisted of medical records of patients of both genders, assisted by professionals qualified by the nipple device, who used them in children aged 03 to 16 years with deleterious habits. The medical records used correspond to patients treated between the years 2000 and 2020. All analyzes were performed in the R program, with a significance level of 5%. Results: 142 medical records were analyzed, in which 122 were included, as they were within the inclusion criteria proposed in the study and 20 were excluded from the research because they presented incomplete information and/or not filled in correctly. The habit with the highest incidence was digital sucking, in 71.3% of patients, 91.8% of patients quit the habit, noting that in cases of pacifier sucking and onychophagia, success in removing the habit was 100%, in both cases. The average time of use of the device was 4.8 months, ranging from 0.6 to 14 months. The mean time to remove the habit after installing the device was 1.6 months, ranging from 0 to 12 months. Conclusion: The nipple device is a highly efficient alternative for removing harmful habits of pacifier, finger, tongue and onychophagy sucking.(AU)

Acute pediatric encephalitis: etiology, course, and outcome of a 12-year single-center immunocompetent cohort.

BACKGROUND: Encephalitis is an uncommon but severe disorder due to an inflammation of the brain parenchyma, usually diagnosed on clinical, laboratory, electroencephalographic, and neuroradiological features. New causes of encephalitis have been reported in recent years, so diagnostic criteria have changed over time. We report on a single-center experience of a pediatric Hospital, the hub of its region, over 12 years (2008-2021), with the evaluation of all children managed for acute encephalitis. METHODS: We retrospectively reviewed clinical, laboratory, neuroradiological, and EEG data from the acute phase and outcome of all immunocompetent patients diagnosed with acute encephalitis. According to the newly proposed criteria for pediatric autoimmune encephalitis, we divided patients into infectious, definite autoimmune, probable autoimmune, and possible autoimmune, and performed a comparison between the different groups. RESULTS: 48 patients (26 females, mean age 4.4 years), 19 with infections, and 29 with autoimmune encephalitis, were included. Herpes simplex virus 1 encephalitis was the most frequently identified etiology followed by anti-NMDA receptor encephalitis. Movement disorders at onset and a longer hospital stay were observed more frequently in autoimmune compared to infectious encephalitis (p p < 0.001 and p = 0.001, respectively). Among the autoimmune group, children who started immunomodulatory treatment earlier (within 7 days from onset) had more frequent complete functional recovery (p = 0.002). CONCLUSIONS: Herpes virus and anti-NMDAR encephalitis are the most frequent etiologies within our cohort. Clinical onset and course are extremely variable. Since early immunomodulatory treatment was associated with a better functional outcome, our data confirm that a timely diagnostic classification in definite, probable, or possible autoimmune encephalitis can help the clinician in a successful therapeutic approach.

Ketamine as advanced second-line treatment in benzodiazepine-refractory convulsive status epilepticus in children.

Status epilepticus (SE) is one of the most common neurological emergencies in children. To date, there is no definitive evidence to guide treatment of SE refractory to benzodiazepines. The main objectives of treatment protocols are to expedite therapeutic decisions and to use fast- and short-acting medications without significant adverse effects. Protocols differ among institutions, and most frequently valproate, phenytoin, and levetiracetam are used as second-line treatment. After failure of first- and second-line medications, admission to the intensive care unit and continuous infusion of anesthetics are usually indicated. Ketamine is a noncompetitive N-methyl-D-aspartate receptor antagonist that has been safely used for the treatment of refractory SE in adults and children. In animal models of SE, ketamine demonstrated antiepileptic and neuroprotective properties and synergistic effects with other antiseizure medications. We reviewed the literature to demonstrate the potential role of ketamine as an advanced second-line agent in the treatment of SE. Pharmacological targets, pathophysiology of SE, and the receptor trafficking hypothesis are reviewed and presented. The pharmacology of ketamine is outlined with related properties, advantages, and side effects. We summarize the most recent and relevant publications on experimental and clinical studies on ketamine in SE. Key expert opinion is also reported. Considering the current knowledge on SE pathophysiology, early sequential polytherapy should include ketamine for its wide range of positive assets. Future research and clinical trials on SE pharmacotherapy should focus on the role of ketamine as second-line medication.

How has the SARS-CoV-2 pandemic changed the epidemiology and management of acute bronchiolitis?

OBJECTIVE: SARS-COV-2 pandemic profoundly impacted acute bronchiolitis epidemiology worldwide, especially respiratory syncytial virus (RSV) diffusion and the burden of disease, with remarkable implications on the management of health resources. We aimed to study the epidemiology and clinical course of bronchiolitis in the past 5 years in our region and to assess the trends that occurred during and after the SARS-COV-2 pandemic. METHODS: We conducted an observational study including all children aged 0-2 years with bronchiolitis admitted to a tertiary children's hospital during the last 5 years. Demographic, clinical, and microbiological data were collected. Comparisons between patient subgroups were carried out. RESULTS: A total of 647 patients admitted for bronchiolitis were included (median age 78 days). Molecular diagnostic tests were performed in 617 patients (95.4%) with RSV detected in 51.5% of patients in prepandemic years and 74.5% in pandemic years. Through the study period, we observed a progressive increase in the number of children requiring respiratory support, RSV infections, and children with a history of prematurity. Conversely, this was not true for mechanical ventilation, duration of respiratory support, intensive care unit admission, and length of stay. CONCLUSIONS: Clinical course and epidemiology of bronchiolitis showed a significant change through the study years with a heavy impact during the 2021-2022 season. The increase in the number of patients requiring respiratory support, although not associated with an increase in mechanical ventilation, may be explained by the higher prevalence of RSV. The change in epidemiology highlights the importance of surveillance systems to monitor RSV circulation, to plan prophylactic strategies, and prepare healthcare systems.

Fetal aortic coarctation: A combination of third-trimester echocardiographic parameters to improve the prediction of postnatal outcome.

Objectives: This study aims to determine a combination of third-trimester echocardiographic parameters for improving the prenatal prediction of coarctation of the aorta (CoA) after birth. Methods: We included all cases of suspected CoA during fetal echocardiography performed in the second and/or third trimester of pregnancy at Gaslini Children's Hospital between January 2010 and December 2020. The last prenatal ultrasound evaluation was reviewed considering most of the echocardiographic criteria were already published for prenatal CoA diagnosis. Associated minor cardiac anomalies, such as a ventricular septal defect, persistent left superior vena cava (PLSCV), and redundant foramen ovale (FO) membrane, as well as postnatal outcomes, were reported. Initial perinatal management was defined based on the risk stratification of CoA during prenatal echocardiography. Neonates were divided into two groups depending on the presence or absence of CoA after birth. Results: A total of 91 fetuses with CoA suspicion were selected, of which 27 (30%) were confirmed with CoA after birth and underwent surgical repair. All cardiac parameters except redundant FO membrane and PLSCV showed a significant correlation with CoA. Statistical analysis confirmed that cardiovascular disproportion with right predominance carries an increased risk for occurrence of CoA, especially if already evident during the ultrasound evaluation in the second trimester. Aortic valve (AV) z-score and distal transverse aortic arch (TAA) z-score resulted as the best predictors of CoA after birth. The best cutoff point for CoA discrimination with ROC analysis was an AV z-score of -1.25 and a distal TAA z-score of -0.37. A total of 46% of those without CoA were diagnosed with a cardiac defect, which was not diagnosed in utero, pulmonary hypertension, or a genetic syndrome. Conclusion: The current criteria for diagnosing CoA in utero allow accurate diagnosis of most severe cases but the rate of false positives remains relatively high for milder cases. A combination of anatomic and functional echocardiographic parameters might be used in stratifying the risk of CoA. We proposed the AV and the TAA diameter z-scores as the best predictors of CoA after birth. In addition, neonates without CoA deserve proper monitoring at birth because prenatal evidence of a significant cardiovascular discrepancy between the right and left cardiac structures has an inherent risk for additional morbidity postnatally.

Sex-Related Differences in Long-Term Outcomes After Early-Onset Myocardial Infarction.

Importance: There is growing awareness of sex-related differences in cardiovascular risk profiles, but less is known about whether these extend to pre-menopausal females experiencing an early-onset myocardial infarction (MI), who may benefit from the protective effects of estrogen exposure. Methods: A nationwide study involving 125 Italian Coronary Care Units recruited 2,000 patients between 1998 and 2002 hospitalized for a type I myocardial infarction before the age of 45 years (male, n = 1,778 (88.9%). Patients were followed up for a median of 19.9 years (IQR 18.1-22.6). The primary composite endpoint was the occurrence of cardiovascular death, non-fatal myocardial re-infarction or non-fatal stroke, and the secondary endpoint of hospitalization for revascularisation by means of a percutaneous coronary intervention (PCI) or coronary artery bypass surgery (CABG). Results: ST-elevation MI was the most frequent presentation among both men and women (85.1 vs. 87.4%, p = ns), but the men had a greater baseline coronary atherosclerotic burden (median Duke Coronary Artery Disease Index: 48 vs. 23; median Syntax score 9 vs. 7; both p < 0.001). The primary composite endpoint occurred less frequently among women (25.7% vs. 37.0%; adjusted hazard ratio: 0.69, 95% CI 0.52-0.91; p = 0.01) despite being less likely to receive treatment with most secondary prevention medications during follow up. Conclusions: There are significant sex-related differences in baseline risk factors and outcomes among patients with early-onset MI: women present with a lower atherosclerotic disease burden and, although they are less frequently prescribed secondary prevention measures, experience better long-term outcomes. Trial Registration: 4272/98 Ospedale Niguarda, Ca' Granda 03/09/1998.

Sudden Onset of Severe Pulmonary Hypertension in a Preterm Infant: A Case Report on the Role of Maternal Use of Serotonin Re-Uptake Inhibitors During Pregnancy and Concurrent Risk Factors.

Persistent pulmonary hypertension of the newborn (PPHN) is a severe condition caused by failed circulatory adaptation at birth. Pulmonary hypertension is most common in full-term infants and rare in preterms, although it is increasingly diagnosed also in extremely preterm infants. Previous studies demonstrated the association between maternal use of selective serotonin re-uptake inhibitors during gestation and pulmonary hypertension. This brief report describes the complex physiopathological correlations that were identified in a case of severe pulmonary hypertension in a fetal growth restricted (FGR) preterm infant, with a history of maternal use of antidepressants during pregnancy. Perinatal factors, triggers and aggravating mechanisms caused a dramatic clinical course. Maternal history of escitalopram therapy throughout pregnancy was noted. Uteroplacental insufficiency, fetal hypoxia, FGR, preeclampsia, preterm delivery, antenatal steroids, and cesarean section were documented as concurrent risk factors. Myocardial immaturity and dysfunction, secondary to FGR and prematurity aggravated the hemodynamic compromise. The short time gap between pharmacological ductal closure and the onset of PPHN may suggest a cause-effect relationship, as observed in previous reports. Placental histopathologic findings are reported.

An example of parenchymal renal sparing in the context of complex malformations due to a novel mutation in the PBX1 gene.

INTRODUCTION: PBX1 encodes the pre-B cell leukemia factor 1, a Three Amino acid Loop Extension (TALE) transcription factor crucial to regulate basic developmental processes. PBX1 loss-of-function variants have been initially described in association with renal malformations in both isolated and syndromic forms. CASE REPORT: Herein, we report a male infant presenting multiple organ malformations (cleidosternal dysostosis, micrognathia, left lung hypoplasia, wide interatrial defect, pulmonary hypertension, total anomalous pulmonary venous return, intestinal malrotation) and carrying the heterozygous de novo c.868C > T (p.Arg290Trp) variant in PBX1. This novel variant affects the highly conserved homeodomain of the protein, leading to a non-conservative substitution and consequently altering its tridimensional structure and DNA-binding capacity. CONCLUSION: So far, PBX1 has been reported in association with a broad spectrum of renal anomalies. However, given the role of this gene in many different developing processes, whole-exome sequencing can detect mutations in PBX1 even in patients with different phenotypes, not necessarily involving the renal primordium. This report presents a novel PBX1 variant with a predicted strong deleterious effect. The mutation leads to a non-conservative substitution in a very highly conserved domain of the protein, thus altering its tertiary structure and DNA-binding capacity.

Long-term outcomes of early-onset myocardial infarction with non-obstructive coronary artery disease (MINOCA).

BACKGROUND: Acute myocardial infarction with non-obstructive coronary artery disease (MINOCA) is frequent in patients experiencing an early-onset MI, but data concerning its long-term prognosis are limited and conflicting. METHODS: The Italian Genetic Study on Early-onset MI enrolled 2000 patients experiencing a first MI before the age of 45 years, and had a median follow-up of 19.9 years. The composite primary endpoint was cardiovascular (CV) death, non-fatal MI, and non-fatal stroke (MACE); the secondary endpoint was rehospitalisation for coronary revascularisation. RESULTS: MINOCA occurred in 317 patients (15.9%) and, during the follow-up, there was no significant difference in MACE rates between them and the patients with obstructive coronary artery disease (MICAD: 27.8% vs 37.5%; adjusted hazard ratio [HR] 0.79, 95% confidence interval [CI] 0.57-1.09;p = 0.15). The CV death rate was lower in the MINOCA group (4.2% vs 8.4%, HR 0.26, 95%CI 0.08-0.86;p = 0.03), whereas the rates of non-fatal reinfarction (17.3% vs 25.4%; HR 0.76, 95%CI 0.52-1.13;p = 0.18), non-fatal ischemic stroke (9.5% vs 3.7%; HR 1.79, 95%CI 0.87-3.70;p = 0.12), and all-cause mortality (14.1% vs 20.7%, HR 0.73, 95%CI 0.43-1.25;p = 0.26) were not significantly different in the two groups. The rate of rehospitalisation for coronary revascularisation was lower among the MINOCA patients (6.7% vs 27.7%; HR 0.27, 95% CI 0.15-0.47;p < 0.001). CONCLUSIONS: MINOCA is frequent and not benign in patients with early-onset MI. Although there is a lower likelihood of CV death,the long-term risk of MACE and overall mortality is not significantly different from that of MICAD patients.