Andrea Magnolato

A common genetic background could explain early-onset Crohn's disease.

Crohns disease (CD) is a multifactorial disease, in which environmental, microbial and genetic factors play important roles. CD is characterized by a chronic granulomatous inflammation by necrotic scarring with aspects of full-thickness wall. In spite of affecting mainly young adults, sometimes, CD can be present in the first year of life (early onset Crohn disease, EOCD) showing an unpredictable course and being often more severe than at older ages. In this paper we propose the hypothesis that EOCD patients should be analyzed using a Mendelian approach with family studies aimed to identify new loci directly involved in the early onset Crohns disease. So we will leave the classic association study approach used until now for the identification of genes responsible for susceptibility to CD and propose linkage family analysis as alternative and powerful tool for the identification of new genetic variants associated with familiar cases of EOCD.

Evaluation of the global lung initiative 2012 reference values for spirometry in African children

Rationale: Despite the high burden of respiratory disease, no spirometry reference values for African children are available. Objectives: Investigate whether the Global Lung Initiative (GLI‐2012) reference values for spirometry are appropriate for children in sub‐Saharan Africa and assess the impact of malnutrition on lung function. Methods: Anthropometry and spirometry were obtained in children aged 6 to 12 years from urban and semiurban schools in three African countries. Spirometry z‐scores were derived using the GLI‐2012 prediction equations for African Americans. Thinness (body mass index z‐score < −2) was a surrogate for malnutrition. Spirometry outcomes were compared with those of African American children from the third National Health and Nutrition Survey. Measurements and Main Results: Spirometry data were analyzed from 1,082 schoolchildren (51% boys) aged 6.0 to 12.8 years in Angola (n = 306), Democratic Republic of the Congo (n = 377), and Madagascar (n = 399). GLI‐2012 provided a good fit with mean (SD) z‐scores of −0.11 (0.83) for FEV1, −0.08 (0.86) for FVC, and −0.07 (0.83) for FEV1/FVC. Because of low scatter, the fifth centile corresponded to −1.3 z‐scores in boys and −1.5 z‐scores in girls. Malnourished African children had a normal FEV1/FVC ratio but significant reductions of ˜0.5 z‐scores (˜5%) in FEV1 and FVC compared with African American peers from the third National Health and Nutrition Survey. Children in Angola had the lowest, and those in Madagascar had the highest, zFEV1 and zFVC. Conclusions: The results of this study support the use of GLI‐2012 reference values for schoolchildren in sub‐Saharan Africa. Malnutrition affects body growth, leading to a proportionately smaller FEV1 and FVC without respiratory impairment, as shown by the normal FEV1/FVC ratio.

Inflammation profile of four early onset Crohn patients.

Crohn disease (CD) is a multifactorial disorder affecting mainly young adults. Sometimes, however, it can present in the first year of life (Early onset Crohn disease (EOCD)) showing an unpredictable course and can often be more severe than at older ages. Some cases have been associated to an underlying primary immunodeficiency such as IL10R deficiency. We studied the functional response to IL-10 and the genotype of IL-10 receptor in four patients with early onset crohn-like colitis. We found an IL10R variant, which may be associated with a decreased response to the cytokine in one patient. Further studies to determine its pathogenic effect should be performed. In addition IL-10 mediated inhibition of LPS-induced TNFα expression was measured in patients monocytes.

Combination of intranasal dexmedetomidine and oral midazolam as sedation for pediatric MRI

passage of the ETT, the length of the bougie should be long enough to accommodate the full length of the ETT as well as extend beyond the proximal end of the tube, so that an assistant can hold it firmly while threading the ETT. In children, one of the commonly used introducer is Cook’s 8 French Frova introducer with a length of 35 cm. It is recommended for ETTs with an internal diameter of 3.5 to 5 mm. The length of a pediatric Frova is adequate when used with endotracheal tubes of internal diameter up to 4.5 mm ID but its length falls short with larger tubes. The average length of 5 mm ID ETT from various manufacturers varies from 24 to 25 cm with the exclusion of the universal circuit adaptor, which makes it impossible to hold the proximal end of introducer once the ETT is railroaded over it (Figure 1). This necessitates discontinuing the current attempt of intubation. As the intubation attempts increase, the risk of airway trauma and desaturation also increases. To ensure smooth railroading of the ETT, the pediatric airway introducer should be at least twice the length of the ETT. Otherwise one simple solution to avoid these problems would be to use a preshortened tube cut to the length appropriate for the age and height of the child. The shortened ETT provides an additional benefit of reducing the airway resistance. Another option is to preload the regular length ETT on the introducer with its bent tip extending just beyond the bevel of ETT. The manufacturer recommends preloading of the ETT over Frova while using as an intubation aid. This technique provides ample length of the introducer beyond the proximal end of the tube but if tube exchange is needed due to improper size, the same problem of inadequate length will crop up; therefore, a shortened tube should be kept standby. This simple step of shortening the ETT while using pediatric Frova introducer can avoid unwanted stress while managing a difficult airway in children and smoothen the process of intubation.

Innovation for rare diseases and bioethical concerns: A thin thread between medical progress and suffering

With the development of precision medicines based on small molecules, antibodies, RNAs and gene therapy, technological innovation is providing some exciting possibilities to treat the most severe genetic diseases. However, these treatments do not always lead to a cure for the disease, and there are several factors that may hinder their overall success. Patients living during a period of great medical change and innovation may benefit from these technological advances but may also just face failures, both in terms of frustrated hopes as well as suffering. In this article, we are telling the stories of three children with rare and severe disorders, who live in an age of significant medical changes, bearing the burden of difficult scientific and ethical choices. The first two cases that are suffering respectively from severe immunodeficiency and beta thalassemia have already been described in scientific journals, as well as in popular magazines. Although similar when considering the medical challenges, the two cases had opposite outcomes, which resulted in distinct ethical implications. The third case is a baby with spinal muscular atrophy, living at a time of continued innovation in the treatment of the disease. With these cases, we discuss the challenges of providing correct information and proper counseling to families and patients that are making the bumpy journey on the road of medical innovation.

When Long-Lasting Food Selectivity Leads to an Unusual Genetic Diagnosis: A Case Report

Hereditary fructose intolerance is an autosomal recessive disorder of fructose metabolism caused by catalytic deficiency of aldolase B enzyme [1]. The disease is typically expressed when fructose- and sucrose-containing foods are first introduced in the diet; acute manifestations include nausea, vomiting, abdominal distress, and symptomatic hypoglycemia [1,2]. Chronic fructose ingestion eventually leads to poor feeding, growth retardation and gradual liver and/or renal failure [3,4]. Some patients may remain undiagnosed until adulthood because of a self-protective avoidance of sweet tasting food that prevents the development of acute toxicity from fructose containing food; however, these subjects may suffer intermittent symptoms throughout life, leading to potentially serious misdiagnosis [4]. We report the case of a patient with unrecognized hereditary fructose intolerance in which chronic gastrointestinal complaints, low body weight, and unexplained food avoidance were addressed as manifestations of an eating disorder during adolescence.

Teaching pain recognition through art: the Ramsay-Caravaggio sedation scale

BackgroundClinical observation is a key component of medical ability, enabling immediate evaluation of the patient’s emotional state and contributing to a clinical clue that leads to final decision making. In medical schools, the art of learning to look can be taught using medical humanities and especially visual arts. By presenting a Ramsay sedation score (RSS) integrated with Caravaggio’s paintings during a procedural sedation conference for pediatric residents, we want to test the effectiveness of this approach to improve the quality of learning.MethodsIn this preliminary study, we presented videos showing sedated pediatric patients in the setting of a procedural sedation lesson to two randomized groups of residents, one attending a lesson on RSS explained through the masterpieces of Caravaggio, the other without artistic support. A week later we tested their learning with ten multi-choice questions focused on theoretical questions about sedation monitoring and ten more questions focused on recognizing the appropriate RSS viewing the videos. The primary outcome was the comparison of the total number of RSS layers properly recognized in both groups. We also evaluated the appreciation of the residents of the use of works of art integrated with the lesson.ResultsEleven students were randomized to each group. Two residents in the standard lesson did not attend the test. The percentage of correct answers on the theoretical part was similar, 82% in the art group and 89% in the other (p > 0.05). No difference was found in the video recognition part of the RSS recognition test. Residents exposed to paintings shown great appreciation for the integration of the lesson with the Caravaggio’s masterpieces.ConclusionsAdding artwork to a standard medical conference does not improve the performance of student tests, although this approach has been greatly appreciated by residents.

Three cases of Bartonella quintana infection in children.

We present 3 children affected by B. quintana infection treated at the IRCCS Burlo Garofolo of Trieste between March and April 2013. B. quintana infection is rare but it should be suspected in patients with fever and lymphadenopathy who do not respond to conventional antibiotic treatment. All patients had a complete recovery without sequelae or relapses.