Search

Abstract 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.

Summary: Background: Gastric cancer (GC) is clinically heterogenous according to location (cardia/non-cardia) and histopathology (diffuse/intestinal). We aimed to characterize the genetic risk architecture of GC according to its subtypes. Another aim was to examine whether cardia GC and oesophageal adenocarcinoma (OAC) and its precursor lesion Barrett’s oesophagus (BO), which are all located at the gastro-oesophageal junction (GOJ), share polygenic risk architecture. Methods: We did a meta-analysis of ten European genome-wide association studies (GWAS) of GC and its subtypes. All patients had a histopathologically confirmed diagnosis of gastric adenocarcinoma. For the identification of risk genes among GWAS loci we did a transcriptome-wide association study (TWAS) and expression quantitative trait locus (eQTL) study from gastric corpus and antrum mucosa. To test whether cardia GC and OAC/BO share genetic aetiology we also used a European GWAS sample with OAC/BO. Findings: Our GWAS consisting of 5816 patients and 10,999 controls highlights the genetic heterogeneity of GC according to its subtypes. We newly identified two and replicated five GC risk loci, all of them with subtype-specific association. The gastric transcriptome data consisting of 361 corpus and 342 antrum mucosa samples revealed that an upregulated expression of MUC1, ANKRD50, PTGER4, and PSCA are plausible GC-pathomechanisms at four GWAS loci. At another risk locus, we found that the blood-group 0 exerts protective effects for non-cardia and diffuse GC, while blood-group A increases risk for both GC subtypes. Furthermore, our GWAS on cardia GC and OAC/BO (10,279 patients, 16,527 controls) showed that both cancer entities share genetic aetiology at the polygenic level and identified two new risk loci on the single-marker level. Interpretation: Our findings show that the pathophysiology of GC is genetically heterogenous according to location and histopathology. Moreover, our findings point to common molecular mechanisms underlying cardia GC and OAC/BO. Funding: German Research Foundation (DFG).

Introduction: Spitzoid lesions are a wide tumour class comprising Spitz nevus (SN), atypical Spitz tumour (AST) and Spitz melanoma (SM). Materials and Methods: We conducted a single-centre-based retrospective survey on all histologically diagnosed spitzoid lesions of paediatric patients (1–18 years) of the last 10 years (2012–2022). Histopathological reports and electronic records of patients were used to retrieve relevant data regarding patients’ features, clinical and dermatoscopical aspects of lesions when recorded, and FISH tests when present. Results: Of 255 lesions, 82% were histologically benign, 17% atypical, 1% malignant. Clinically, 100% of SM were large (≥6 mm) and raised; AST were mainly large (63%), raised (98%), pink (95%). Small (≤5 mm), pigmented, flat lesions correlated with benign histology (respectively 90%, 97%, 98% SN) (p < 0.0001). Dermatoscopical patterns were analysed in 100 patients: starburst pattern correlated with benign histology (26% SN (p = 0.004)), while multicomponent pattern correlated with atypical/malignant lesions (56% AST, 50% SM (p = 0.0052)). Eighty-five lesions were subjected to fluorescence in situ hybridization (FISH): 34 (71% AST; 29% SN) were FISH-positive; 51 (63% SN; 37% AST) were FISH-negative (p = 0.0038). Discussion: This study confirmed predominant benign histology (82%) of paediatric spitzoid lesions, thus detecting 17% AST and 1% SM, highlighting the need for caution in handling spitzoid lesions. Conclusion: Until AST are considered potentially malignant proliferations and no reliable criteria are identified to distinguish them, the authors suggest a prudent approach, especially in children.

La película “Casas de Fuego” de Juan Bautista Stagnaro es un recurso difundido en la enseñanza del Chagas en distintos niveles. A más de 25 años de su estreno, nuestro interés en revisitar el uso didáctico del largometraje se originó en una investigación sobre la formación de grado en Chagas en carreras biomédicas de la Universidad Nacional de Río Cuarto (Córdoba, Argentina). En dicho estudio, hallamos referencias espontáneas a “Casas de Fuego” tanto en entrevistas con estudiantes, como en clases observadas. A partir de este resultado “emergente” realizamos una nueva mirada sobre las potencialidades y limitaciones de la película para abordar y comprender el Chagas en la actualidad. En este artículo presentamos resultados del análisis y algunas reflexiones como aporte para actualizar y complementar la utilización de “Casas de Fuego” en las aulas.

OBJECTIVES: To prospectively evaluate demographic, anthropometric and health-related quality of life (HRQoL) in pediatric patients with laboratory-confirmed coronavirus disease 2019 (COVID-19) METHODS: This was a longitudinal observational study of surviving pediatric post-COVID-19 patients (n=53) and pediatric subjects without laboratory-confirmed COVID-19 included as controls (n=52) was performed. RESULTS: The median duration between COVID-19 diagnosis (n=53) and follow-up was 4.4 months (0.8-10.7). Twenty-three of 53 (43%) patients reported at least one persistent symptom at the longitudinal follow-up visit and 12/53 (23%) had long COVID-19, with at least one symptom lasting for >12 weeks. The most frequently reported symptoms at the longitudinal follow-up visit were headache (19%), severe recurrent headache (9%), tiredness (9%), dyspnea (8%), and concentration difficulty (4%). At the longitudinal follow-up visit, the frequencies of anemia (11% versus 0%, p=0.030), lymphopenia (42% versus 18%, p=0.020), C-reactive protein level of >30 mg/L (35% versus 0%, p=0.0001), and D-dimer level of >1000 ng/mL (43% versus 6%, p=0.0004) significantly reduced compared with baseline values. Chest X-ray abnormalities (11% versus 2%, p=0.178) and cardiac alterations on echocardiogram (33% versus 22%, p=0.462) were similar at both visits. Comparison of characteristic data between patients with COVID-19 at the longitudinal follow-up visit and controls showed similar age (p=0.962), proportion of male sex (p=0.907), ethnicity (p=0.566), family minimum monthly wage (p=0.664), body mass index (p=0.601), and pediatric pre-existing chronic conditions (p=1.000). The Pediatric Quality of Live Inventory 4.0 scores, median physical score (69 [0-100] versus 81 [34-100], p=0.012), and school score (60 [15-100] versus 70 [15-95], p=0.028) were significantly lower in pediatric patients with COVID-19 at the longitudinal follow-up visit than in controls. CONCLUSIONS: Pediatric patients with COVID-19 showed a longitudinal impact on HRQoL parameters, particularly in physical/school domains, reinforcing the need for a prospective multidisciplinary approach for these patients. These data highlight the importance of closer monitoring of children and adolescents by the clinical team after COVID-19.

The objectives of the study were to calculate the standardised mortality rates (SMRs) for COVID-19 in European Union/European Economic Area countries plus the UK and Switzerland and to evaluate the correlation between SMRs and selected indicators in the first versus the subsequent waves until 23 June 2021. We used indirect standardisation (using Italy as the reference) to compute SMRs and considered 16 indicators of health and social well-being, health system capacity and COVID-19 response. The highest SMRs were in Belgium, the UK and Spain in the first wave (1.20–1.84) and in Hungary, Czechia and Slovakia in the subsequent waves (2.50–2.69). Human Development Index (HDI), life expectancy, urbanisation and healthcare expenditure had positive correlations with SMR in the first wave (rho=0.30–0.46), but negative correlations (rho=−0.67 to −0.47) in the subsequent waves. Retail/recreation mobility and transit mobility were negatively correlated with SMR in the first wave, while transit mobility was inversely correlated with SMR in the subsequent waves. The first wave hit most hard countries with high HDI, high life expectancy, high urbanisation, high health expenditures and high tourism. This pattern may reflect higher early community seeding and circulation of the virus. Conversely, in the subsequent waves, this pattern was completely inversed: countries with more resources and better health status did better than eastern European countries. While major SMR differences existed across countries in the first wave, these differences largely dissipated by 23 June 2021, with few exceptions.

Lung ultrasound is a reasonable tool for detection of manifestations of COVID-19, to facilitate the division of patients flow of infected with SARS-CoV-2 from those affected by other pathologies. Often, a reason for the incorrect separation of the flows is the possibility of false-negative rRT-PCR results. We aimed to evaluate the advantages of performing Lung Ultrasound (LUS) in patients with a negative swab, to confirm the suspicious of COVID-19 at the bedside, according to the recent findings of typical lung ultrasound lesions of COVID19 related pneumonia. We analyzed 11 non-critical patients admitted to Emergency Department in the Internal Medicine ward, during outbreak, as Covid-19 negative patients affected by pneumonia. The result of the ultrasound findings conditioned the consequent allocation of the patient. 9/11 patients had typical LUS findings for COVID-19, but only 3/11 patients had a second positive nasopharyngeal swab, and 2/11 had positive swab on pleural fluid. 6/11 patients remained negative with strongly suspicious LUS lesions, and so treated and isolated as Covid-19 positive. 2/11 had negative swab and none LUS findings, thus treated as affected by other pathologies. These findings clearly show how LUS plays an important role together with the chest x-ray in identifying patients with interstitial pneumonia from COVID-19.

Background: Mutations in genes encoding one of the subunits of succinate dehydrogenase (SDH) are involved in pheochromocytoma (PHEO) and paraganglioma (PGL) development. Over the last few years, such mutations have also been associated with non-chromaffin tumors. However, immunohistochemistry (IHC) on the tumor tissue and a study on the loss of heterozygosity (LOH) aimed at demonstrating the pathogenic role of SDHx genes have only been employed in a few cases. Case report: We describe the case of a 19-year-old Caucasian man with a germline SDHB mutation, who presented with acne vulgaris resistant to medical treatment. His follow-up for chromaffin tumors was negative, while hormonal tests revealed suppressed gonadotropins with testosterone in the upper range of normality and elevated β-human chorionic gonadotropin (β-hCG). At the whole-body enhanced CT scan, a mediastinal lesion suggestive of a germ cell tumor (GCT) was detected. 18FDG-PET (fluorodeoxyglucose-positron emission tomography) imaging showed low glucose metabolism at the mediastinal site. Surgical removal of the mass was uneventful. Pathology confirmed the diagnosis of GCT consisting of cystic teratoma (95%) and seminoma (5%). IHC for SDHB showed normal protein expression, and genetic analysis of the tumor tissue revealed the absence of SDHB LOH. Normalization of the hormonal tests and acne attenuation were achieved after surgery. Conclusion: We report an incidental association of a germinal SDHB mutation and mediastinal GCT in a young Caucasian man. Our paper highlights the importance of IHC and genetic analysis in confirming the etiologic role of SDHx genes in nonchromaffin tumors, thus excluding incidental associations.

Psychogenic non-epileptic seizures (PNES) or dissociative seizures are found under the umbrella headings of functional/dissociative neurological disorders (FND) in psychiatric classifications (DSM-5; ICD-11). PNES are not characterized by any specific ictal or postictal EEG abnormalities. Patients with PNES can present with motor or non-motor symptoms, frequently associated with a change in the level of consciousness. PNES duration is variable, often longer than that of epileptic seizures. Prolonged PNES, sometimes termed PNES status, involve continuous or repetitive events that exceed 30 min. Prolonged PNES are often misdiagnosed as an epileptic event and are often inappropriately treated with high doses of antiseizure drugs. In this report, we describe two adolescent patients who presented with prolonged PNES characterized by generalized hypertonic posturing and low levels of consciousness. Despite multiple presentation to the Emergency department, and multiple normal video-EEG, the patients were misdiagnosed with epilepsy and were inappropriately treated with antiseizure medications. Both patients presented psychiatric comorbidity, consisting of a major depressive disorder, obsessive-compulsive symptoms, social withdrawal, difficulty of social interaction, and anxious-perfectionist personality traits. The episodes of prolonged PNES gradually declined within 18 months in both patients.

A large body of literature reports the higher prevalence of epilepsy in subjects with Autism Spectrum Disorder (ASD) compared to the general population. Similarly, several studies report an increased rate of Subclinical Electroencephalographic Abnormalities (SEAs) in seizure-free patients with ASD rather than healthy controls, although with varying percentages. SEAs include both several epileptiform discharges and different non-epileptiform electroencephalographic abnormalities. They are more frequently associated with lower intellectual functioning, more serious dysfunctional behaviors, and they are often sign of severer forms of autism. However, SEAs clinical implications remain controversial, and they could represent an epiphenomenon of the neurochemical alterations of autism etiology. This paper provides an overview of the major research findings with two main purposes: to better delineate the state-of-the-art about EEG abnormalities in ASD and to find evidence for or against appropriateness of SEAs pharmacological treatment in ASD.

Background: Although screening programmes of smokers have detected resectable early lung cancers more frequently than expected, their efficacy in reducing mortality remains debatable. To elucidate the biological features of computed tomography (CT) screening detected lung cancer, we examined the mRNA signatures on tumours according to the year of detection, stage and survival. Methods: Gene expression profiles were analysed on 28 patients (INT–IEO training cohort) and 24 patients of Multicentre Italian Lung Detection (MILD validation cohort). The gene signatures generated from the training set were validated on the MILD set and a public deposited DNA microarray data set (GSE11969). Expression of selected genes and proteins was validated by real-time RT-PCR and immunohistochemistry. Enriched core pathway and pathway networks were explored by GeneSpring GX10. Findings: A 239-gene signature was identified according to the year of tumour detection in the training INT–IEO set and correlated with the patients' outcomes. These signatures divided the MILD patients into two distinct survival groups independently of tumour stage, size, histopathological type and screening year. The signatures can also predict survival in the clinically detected cancers (GSE11969). Pathway analyses revealed tumours detected in later years enrichment of the PI3K/PTEN/AKT pathway, with up-regulation of PDPK1, ITGB1 and down-regulation of FOXO1A. Analysis of normal lung tissue from INT–IEO cohort produced signatures distinguishing patients with early from late detected tumours. Interpretation: The distinct pattern of “indolent” and “aggressive” tumour exists in CT-screening detected lung cancer according to the gene expression profiles. The early development of an aggressive phenotype may account for the lack of mortality reduction by screening observed in some cohorts.

Rajesh Mukthavaram,1 Pengfei Jiang,1 Rohit Saklecha,1 Dmitri Simberg,3,4 Ila Sri Bharati,1 Natsuko Nomura,1 Ying Chao,1 Sandra Pastorino,1 Sandeep C Pingle,1 Valentina Fogal,1 Wolf Wrasidlo,1,2 Milan Makale,1,2 Santosh Kesari1,21Translational Neuro-Oncology Laboratories, 2Department of Neurosciences, 3Solid Tumor Therapeutics Program, Moores Cancer Center, UC San Diego, La Jolla, CA, 4Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado, Denver, CO, USAAbstract: Staurosporine (STS) is a potent pan-kinase inhibitor with marked activity against several chemotherapy-resistant tumor types in vitro. The translational progress of this compound has been hindered by poor pharmacokinetics and toxicity. We sought to determine whether liposomal encapsulation of STS would enhance antitumor efficacy and reduce toxicity, thereby supporting the feasibility of further preclinical development. We developed a novel reverse pH gradient liposomal loading method for STS, with an optimal buffer type and drug-to-lipid ratio. Our approach produced 70% loading efficiency with good retention, and we provide, for the first time, an assessment of the in vivo antitumor activity of STS. A low intravenous dose (0.8 mg/kg) inhibited U87 tumors in a murine flank model. Biodistribution showed preferential tumor accumulation, and body weight data, a sensitive index of STS toxicity, was unaffected by liposomal STS, but did decline with the free compound. In vitro experiments revealed that liposomal STS blocked Akt phosphorylation, induced poly(ADP-ribose) polymerase cleavage, and produced cell death via apoptosis. This study provides a basis to explore further the feasibility of liposomally encapsulated STS, and potentially related compounds for the management of resistant solid tumors.Keywords: liposomes, staurosporine, glioblastoma, biodistribution, efficacy

OBJECTIVES: To determine possible variations in the Anthropometric Index for pectus excavatum relative to age, race, and sex in individuals free of thoracic wall deformities. METHODS: Between 2002 and 2012, 166 individuals with morphologically normal thoracic walls consented to have their chests and the perimeter of the lower third of the thorax measured according to the Anthropometric Index for pectus excavatum. The participant characteristics are presented (114 men and 52 women; 118 Caucasians and 48 people of African descent). RESULTS: Measurements of the Anthropometric Index for pectus excavatum were statistically significantly different between men and women (11-40 years old); however, no significant difference was found between Caucasians and people of African descent. For men, the index measurements were not significantly different across all of the age groups. For women, the index measurements were significantly lower for individuals aged 3 to 10 years old than for individuals aged 11 to 20 years old and 21 to 40 years old; however, no such difference was observed between women aged 11 to 20 years old and those aged 21 to 40 years old. CONCLUSION: In the sample, significant differences were observed between women aged 11 to 40 years old and the other age groups; however, there was no difference between Caucasian and people of African descent.

OBJECTIVES: The aim of this cross-sectional study was to evaluate whether interleukin 10 (IL10) and transforming growth factor β1 (TGFβ1) gene polymorphisms were associated with persistent IgE-mediated cow's milk allergy in 50 Brazilian children. The diagnostic criteria were anaphylaxis triggered by cow's milk or a positive double-blind, placebo-controlled food challenge. Tolerance was defined as the absence of a clinical response to a double-blind, placebo-controlled food challenge or cow's milk exposure. METHOD: The genomic DNA of the 50 patients and 224 healthy controls (HCs) was used to investigate five IL10 gene polymorphisms (-3575A/T, -2849A/G, -2763A/C, -1082G/A, -592C/A) and one TGFβ1 polymorphism (-509C/T). RESULTS: Among the five IL10 polymorphisms analyzed, homozygosis for the G allele at the -1082 position was significantly higher in the patients compared with the healthy controls (p = 0.027) and in the persistent cow's milk allergy group compared with the healthy controls (p = 0.001). CONCLUSIONS: Homozygosis for the G allele at the IL10 -1082G/A polymorphism is associated with the persistent form of cow's milk allergy.

The detection of a low serum phosphate level is not unusual in an Emergency Department, especially in clinical conditions linked to hyperventilation and subsequent respiratory alkalosis, asthma, sepsis, severe pain, anxiety. Symptoms of hypophosphatemia are typically not specific when the imbalance is not particularly severe, but if hyphophosphatemia does not resolve rhabdomyolisis, hemolysis, decreased tissue oxygenation and respiratory failure can be observed. Only recently some authors have pointed out that the level of serum phosphate in patient with anxiety and panic disorders can give information on the severity of the attacks as well on the clinical course of the disease. In a retrospective analysis on 599 case of hypophosphatemia observed in our ED, the percentage of case of panic disorders was particularly high among patients with lower phosphatemia. Therefore, we decided to examine this aspect closely, assessing if the determination of serum phosphate could be useful in the management of panic attacks at first approach in emergency room. Our observation are consistent with the statement that hypophosphatemia is one of the main clinical aspect of panic attack, and strongly support the hypothesis that hypophosphatemia correlates with the most severe symptoms of panic attack and should be itself considered as one of the most important aspect of this syndrome. Serum phosphate levels appear to mirror its clinical course, and can be used in the clinical setting of an Emergency Department, for the confirmation of a diagnosis of anxiety-panic disorder and as marker of the response to therapy

The aims of the present work were the evaluation of allergic disease prevalence among 6 and 7 year-old students from the western districts of São Paulo city and the comparison of these data with those obtained in the International Study of Asthma and Allergies in Childhood (ISAAC) phase I, performed in the central-southern districts of São Paulo, using the ISAAC standardized written questionnaire. METHODS: 5,040 questionnaires were distributed and 3,312 were returned. Proportional differences were estimated by Chi square or Fisher exact tests. Odds Ratio and 95% confidence intervals between genders and allergic diseases were calculated. Values of pOBJETIVOS: Avaliar a prevalência das doenças alérgicas na região oeste de São Paulo entre escolares de 6 a 7 anos e comparar os dados obtidos com aqueles da fase I da região centro-sul, através do questionário padronizado do International Study of Asthma and Allergies in Childhood. MÉTODOS: Foram enviados 5040 questionários escritos com resposta de 3.312 alunos. As diferenças entre proporções foram avaliadas pelo Teste do Qui-quadrado ou Teste Exato de Fisher, se calculado a Razão das Chances, intervalo de confiança 95% entre os sexos e doenças alérgicas. Os valores de p < 0,05 foram considerados como significantes. RESULTADOS: As prevalências corrigidas encontradas foram: asma 24,4%, diagnóstico médico de asma 5,7%, rinite 25,7%, rinoconjuntivite 11,3%, diagnóstico médico de rinite 20%, eczema atópico 9,2%. Houve associação significativa entre asma e rinite (OR=3,3), asma e eczema (OR=2,2) e rinite e eczema atópico (OR=2,8). O sexo masculino foi predominante para asma e rinite. Comparando-se os dados da fase I, observou-se prevalência mais elevada dos sintomas e gravidade de asma e valores menores para rinite e eczema. CONCLUSÕES: As prevalências de asma e rinite neste estudo mostraram valores elevados em comparação ao diagnóstico médico. Houve predomínio do sexo masculino para asma e rinite. As associações mais freqüentes foram entre asma e rinite e asma e eczema. Em relação à região centro-sul de São Paulo, observou-se que na região oeste houve maior prevalência dos sintomas e gravidade da asma e menor prevalência de rinite e eczema.

Syncope is a common clinical entity, and it causes up to 3% of admission in the Emergency Department. The evaluation of syncope begins with a careful history, physical examination, and electrocardiography, with a correct identification of etiology at the presentation in up to 50% of cases. Moreover, the underlying cause of syncope remains unidentified in a elevated percentage of patients. The application of Standard Guidelines and the institution of the Observation Unit (OBI) with continuous monitoring improves patients management, chiefly in the geriatric population (> 65 years old). In older patients the clinical features of syncope are less defined, and the medical history has a limited value. The management in the OBI of this group of patient with continuous monitoring could become the best approach. The ECG monitoring can detect life-threatening arrhythmias in older patients with apparent non cardiac syncope. In the firs six months of 2005 the Emergency Department of the Ospedale San Paolo (Savona) evaluated 164 patients > 65 years old with diagnosis of syncope/pre-syncope. During monitoring we detected events of arrhythmia in 12 patients (7,3%), including ventricular tachycardia in 2, atrial fibrillation in 4, paroxysmal atrial flutter in 2, paroxysmal supraventricular tachycardia in 1, asystole in 1 and third-degree atrioventricular block in 2 patients. We briefly describe 2 of this case: in both cases the first suggestion indicates a possible non cardiac etiology, but the subsequent monitoring shows episodes of potentially fatal arrhythmia. Both an early discharge and an in non-monitorized bed admission wouldn’t have preserved the two patient by a sudden cardiac death.

Antecedentes: la exposición a factores psicosociales en el trabajo, como la demanda o exigencias psicológicas, el control sobre las tareas y el apoyo social en el ambiente laboral guardan relación con el estrés y su repercusión en la salud mental. El propósito de este trabajo ha sido estimar la prevalencia de dicho síndrome en un grupo de trabajadores de un hospital de la ciudad de Santiago (Chile) y analizar la posible asociación entre los factores psicosociales nombrados y el Síndrome de Burnout. Diseño: de tipo transversal. Muestra: de tipo no probabilística, donde los casos fueron seleccionados por conveniencia (n = 416) Instrumentos : Escala de Efectos Psíquicos de Burnout (EPB), Cuestionario de Salud General de Goldberg (GHQ-28) y Cuestionario para la evaluación de riesgos psicosociales en el trabajo ISTAS 21. Métodos: se calculó la prevalencia de Burnout a partir del método de conglomerados k-medias y se construyó un modelo de regresión logística. Resultados: la prevalencia de trabajadores con Burnout fue del 25% y se encontró una asociación significativa con mayores niveles de exigencias psicológicas, así como con una interacción entre apoyo social y control en las tareas. Conclusiones: el síndrome de Burnout está asociado a los tres factores psicosociales del modelo demanda-control-apoyo social.

Summary: Background: Neuroblastoma (NB) represents the most frequent form of extra-cranial solid tumour of infants, responsible for 15% of childhood cancer deaths. Nucleolin (NCL) prognostic value in NB was investigated. Methods: NCL protein expression was retrospectively evaluated in tumour samples of NB patients at diagnosis and after chemotherapy. NCL prognostic value at mRNA level was assessed in a cohort of 20 patients with stage 4 NB (qPCR20, n=20, discovery dataset) and in the MultiPlatform786 including 786 patients of all stages (validation dataset). Overall and event-free survival curves were plotted by Kaplan-Meier method and compared by log-rank test. Findings: NCL protein, down-modulated after chemotherapy in association with features of neuroblastic differentiation,resulted statistically significantly overexpressed in NB tumours and higher in stage 4 compared to stage 1,2,3 patients. In the stage 4 patients cohort qPCR20, patients with high NCLmRNA expression revealed a statisticallysignificant lower survival probability than those with low NCL expression (OS: HR 4.1 95%CI 1.2–13.8;p=0.0215[Log-rank test], EFS: HR 4.1 95%CI 1.2–14.0, p=0.0197[Log-rank test]). In the MultiPlatform786 (n=786), multivariate analysis suggested thatNCL expression has a statistically significant prognostic value even in the model adjusted for established prognostic markers. NCL expression significantly stratified also patients with >18 months and stage 4 tumour (OS: HR 1.8 95%CI 1.2–2.7, p=0.0009[Log-rank test]; EFS: HR 1.7 95%CI 1.1–2.5, p=0.002[Log-rank test]), patients with>18 months stage 4 with MYCN non amplified tumour[EFS: HR 2.3 95%CI 1.2–4.7, p=0.01[Log-rank test]), and patients with MYCN non amplified and MYC high [OS: HR 11.9 95%CI 2.3–62.4, p=0.003[Log-rank test]; EFS: HR 7.2 95%CI 1.6–33.4, p=0.01[Log-rank test]). A statistically significant correlation between NCL and MYCN, MYC, and TERT was found in independent datasets (MultiPlatform786 (n=786) and Agilent394 (n=394). Gene set enrichment analysis revealed a statisticallysignificant positive enrichment of MYC target genes and genes involved in telomerase maintenance. Interpretation: NCL is a novel and independent (adjusting for age, INSS stage, and MYCN status) prognostic marker for NB. Funding: IMH-EuroNanoMed II-2015 and AIRC-IG.

This study aims to compare the low-dose computed tomography (LDCT) outcome and volume-doubling time (VDT) derived from the measured volume (MV) and estimated volume (EV) of pulmonary nodules (PNs) detected in a single-center lung cancer screening trial. MV, EV and VDT were obtained for prevalent pulmonary nodules detected at the baseline round of the bioMILD trial. The LDCT outcome (based on bioMILD thresholds) and VDT categories were simulated on PN- and screenee-based analyses. A weighted Cohen’s kappa test was used to assess the agreement between diagnostic categories as per MV and EV, and 1583 screenees displayed 2715 pulmonary nodules. In the PN-based analysis, 40.1% PNs were included in different LDCT categories when measured by MV or EV. The agreements between MV and EV were moderate (κ = 0.49) and fair (κ = 0.37) for the LDCT outcome and VDT categories, respectively. In the screenee-based analysis, 46% pulmonary nodules were included in different LDCT categories when measured by MV or EV. The agreements between MV and EV were moderate (κ = 0.52) and fair (κ = 0.34) for the LDCT outcome and VDT categories, respectively. Within a simulated lung cancer screening based on a recommendation by estimated volumetry, the number of LDCTs performed for the evaluation of pulmonary nodules was higher compared with in prospective volumetric management.

Lung cancer (LC) is currently one of the main causes of cancer-related deaths worldwide. Low-dose computed tomography (LDCT) of the chest has been proven effective in secondary prevention (i.e., early detection) of LC by several trials. In this work, we investigated the potential impact of radiomics on indeterminate prevalent pulmonary nodule (PN) characterization and risk stratification in subjects undergoing LDCT-based LC screening. As a proof-of-concept for radiomic analyses, the first aim of our study was to assess whether indeterminate PNs could be automatically classified by an LDCT radiomic classifier as solid or sub-solid (first-level classification), and in particular for sub-solid lesions, as non-solid versus part-solid (second-level classification). The second aim of the study was to assess whether an LCDT radiomic classifier could automatically predict PN risk of malignancy, and thus optimize LDCT recall timing in screening programs. Model performance was evaluated using the area under the receiver operating characteristic curve (AUC), accuracy, positive predictive value, negative predictive value, sensitivity, and specificity. The experimental results showed that an LDCT radiomic machine learning classifier can achieve excellent performance for characterization of screen-detected PNs (mean AUC of 0.89 ± 0.02 and 0.80 ± 0.18 on the blinded test dataset for the first-level and second-level classifiers, respectively), providing quantitative information to support clinical management. Our study showed that a radiomic classifier could be used to optimize LDCT recall for indeterminate PNs. According to the performance of such a classifier on the blinded test dataset, within the first 6 months, 46% of the malignant PNs and 38% of the benign ones were identified, improving early detection of LC by doubling the current detection rate of malignant nodules from 23% to 46% at a low cost of false positives. In conclusion, we showed the high potential of LDCT-based radiomics for improving the characterization and optimizing screening recall intervals of indeterminate PNs.

INTRODUCTION: The DiGeorge Syndrome was first described in 1968 as a primary immunodeficiency resulting from the abnormal development of the third and fourth pharyngeal pouches during embryonic life. It is characterized by hypocalcemia due to hypoparathyroidism, heart defects, and thymic hypoplasia or aplasia. Its incidence is 1:3000 live births and, despite its high frequency, little is known about its natural history and progression. ←This is probably due to diagnostic difficulties and the great variety of names used to describe it, such as velocardiofacial, Shprintzen, DiGeorge, and CATCH 22 Syndromes, as well as conotruncal facial anomaly. All represent the same genetic condition, chromosome 22q11.2 deletion, which might have several clinical expressions. OBJECTIVES: To describe clinical and laboratorial data and phenotypic characteristics of patients with DiGeorge Syndrome. METHODS: Patients underwent standard clinical and epidemiological protocol and tests to detect heart diseases, facial abnormalities, dimorphisms, neurological or behavioral disorders, recurrent infections and other comorbidities. RESULTS: Of 14 patients (8m - 18y11m), only one did not have 22q11.2 deletion detected. The main findings were: conotruncal malformation (n = 12), facial abnormalities (n = 11), hypocalcemia (n = 5) and low lymphocyte count (n=2). CONCLUSION: The authors pointed out the necessity of DGS suspicion in all patient presenting with heart defects, facial abnormalities (associated or not with hypocalcemia), and immunological disorders because although frequency of DGS is high, few patients with a confirmed diagnosis are followed up.