Bronchiolitis – It Is Time for a Unique Definition

Bronchiolitis is the most common lower respiratory tract infections in infants. It is time to reach a unique clinical definition, encompassing the acute onset of respiratory distress with cough, tachypnoea, retraction and diffuse crackles on auscultation in infants aged less than 12 months

Application de la mécanique des fluides numérique à l'imagerie de la pathologie de l'aorte thoracique et des traitements endovasculaires modernes par pose d'endoprothèse

La prise en charge des malades porteurs de maladie de l'aorte thoracique a été révolutionnée pendant ces dernières années par l'introduction du traitement endovasculaire par implantation d'endoprothèse, présenté à la communauté scientifique sur le New England Journal of Medicine en 1994. Depuis ce temps, une multitude d'études ont alimenté la littérature scientifique spécialisée. Cependant, même si les résultats cliniques ont étés encourageants au point de proposer la nouvelle thérapie comme référence dans certaines indications, notamment en cas d'urgence, moins d'attention a été réservée aux conséquences fonctionnelles liées à la pose du dispositif à l'intérieur du vaisseau. A partir de l'état vasculaire natif, quelles sont les modifications induites par l'endoprothèse sur l'anatomie et l'hémodynamique de l'aorte ? Cette question est le fil conducteur de mon projet de recherche. J'aborde dans cette thèse l'ensemble des problèmes liés au rôle de l'imagerie vasculaire fonctionnelle dans la prise en charge du patient aux différentes étapes de la méthodologie développée. Les simulations hémodynamiques par application de la mécanique des fluides numérique (MFN) sont, à ce jour, la seule méthode proposée pour obtenir une imagerie fonctionnelle de l'aorte thoracique pour l'évaluation des endoprothèses. En comptant sur une solide expérience au sein du laboratoire OCFIA avec la fusion des techniques d'imagerie classiques et la MFN, l'objectif des travaux de cette thèse de science est le développement de la filière de recherche dédiée à l'application de la mécanique des fluides numérique pour l'exploration hémodynamique de l'aorte thoracique et des conséquences des nouveaux traitements endovasculaires par implantation d'endoprothèse. Le projet a été structuré en deux axes : le premier a été focalisé sur l'évaluation d'une méthode d'imagerie fonctionnelle visant la reconstruction de conditions réalistes et spécifiques à l'aide du couplage entre l'imagerie par résonance magnétique (IRM) et la MFN. La méthodologie, mise au point au sein du laboratoire OCFIA, permet d'obtenir des vraies cartographies hémodynamiques centrées sur des paramètres différents, notamment la vitesse, la vorticité du flux et la force de cisaillement pariétal. La participation des médecins de l'équipe a permis de vérifier la faisabilité de la méthode in vivo et de comparer les études fonctionnelles aux données anatomiques pour en évaluer la fiabilité. Le deuxième axe du projet a été conçu pour développer l'application de la MFN à la recherche clinique. Dans ce but, le code Xflow a été choisi pour le couplage avec le scanner afin de réaliser une analyse quantitative de deux paramètres (le WSS et la vorticité), sur une série de 30 patients pour mettre en évidence les éventuelles modifications de l'état fonctionnel aortique avant et après mise en place d'endoprothèse. Le développement de la méthode scanner-MFN a permis d'évaluer, dans un premier temps, l'impact anatomique de l'implantation sur 60 géométries aortiques, un travail original dans le cadre de la littérature spécialisée. Ensuite, la base des données a été exploitée pour obtenir les simulations numériques à l'aide de différents outils à l'intérieur du logiciel solveur. Une extraction ponctuelle a été réalisée sur les zones d'implantation, permettant de confirmer l'hypothèse concernant les conséquences fonctionnelles du traitement sur le vaisseau natif. La publication des travaux dans des revues internationales incite les futurs développements pour optimiser l'application de nouvelles méthodes à la recherche clinique afin d'individualiser le rôle des facteurs fonctionnels soit dans le contexte du suivi des patients, soit dans l'évaluation de l'efficacité des dispositifs.Since 1994, when thoracic endovascular aortic repair (TEVAR) was presented to the medical community on the New England Journal of Medicine, the management of the aortic pathologies has dramatically changed in favour of a less invasive treatment associated with lower mortality and morbidity rates. A multitude of clinical trials, institutional registers and case reports has enriched the scientific literature and consecrated the new therapy which has been recently proposed as the new gold standard for such a theatre as the acute traumatic aortic rupture (ATAR). Nevertheless, little is known about the consequences of the device implantation on the native aortic status, in term either of anatomy and function. All routinely available techniques certainly provide well-detailed analysis of the aortic morphology but, so far, none of them allows for a functional exploration of the post-implantation status of the patients treated by TEVAR. The purpose of this PhD project, run over three years, was to develop functional vascular imaging techniques based on the combination of magnetic resonance (MR) and computed tomography (CT) with the CFD technology for the analysis of the thoracic aortic haemodynamics before and after the implantation of an endograft. Two main research lines have been followed: the first one was focused on the MRI-CFD combination for performing virtual simulations of the flow behaviour based on realistic patient-specific conditions. The multidisciplinary team of the OCFIA research laboratory implemented the methodology that was tested in vivo for the application in the thoracic aorta. Three-dimensional functional maps of the flow patterns were obtained and different parameters such as the velocity, vorticity and wall shear stress were qualitatively analyzed. The functional maps were compared with the morphologic images to assess their reliability. The second research line was dedicated to the application of the CFD-vascular imaging to a clinical study. The Xflow code was used with a CT combined approach for a systematic quantitative evaluation on a series of 30 patients; pre and post operative geometries were extracted and analyzed in order to detect the anatomical modifications before and after the implantation. The 3D image dataset was thereafter used for launching the CFD runs by a lagrangian approach. A quantitative comparative analysis of the wall shear stress and the vorticity was focused on the landing zones by means of two different tools. The outcomes confirmed the hypothesis of the impact of the endovascular treatment on the aortic status in terms of anatomy and functional changes. The application of the CFD methods for the functional evaluation of the thoracic aorta appeared feasible both before and after a stent-graft implantation. Over the three years two different papers have been accomplished and gained attention for publication on international journals. An implementation of the techniques is necessary to develop the clinical application of the CFD methods and weigh up their role in the whole patient management

Delayed eruption of permanent dentition and maxillary contraction in patients with cleidocranial dysplasia: review and report of a family

Introduction. Cleidocranial dysplasia (CCD) is an inherited disease caused by mutations in the RUNX2 gene on chromosome 6p21. This pathology, autosomal dominant or caused by a spontaneous genetic mutation, is present in one in one million individuals, with complete penetrance and widely variable expressivity. Aim. To identify the incidence of these clinical findings in the report of the literature by means of PubMed interface from 2002 to 2015, with the related keywords. The report of local patients presents a clinical example, related to the therapeutic approach. Results and Discussions. The PubMed research resulted in 122 articles. All the typical signs were reported in all presented cases. The maxilla was hypoplastic in 94% of the patients. Missing of permanent teeth was found in two cases: one case presented a class II jaw relationship, instead of class III malocclusion. Similar findings were present in our cohort. Conclusion. CCD is challenging for both the dental team and the patient. The treatment requires a multidisciplinary approach. Further studies are required to better understand the cause of this disease. According to this review, a multistep approach enhances the possibilities to achieve the recovery of the most possible number of teeth, as such to obtain a good occlusion and a better aesthetic

Gelatin tannate for acute childhood gastroenteritis: a randomized, single-blind controlled trial

Background Oral rehydration therapy is the recommended treatment for acute childhood gastroenteritis. The aim of this study was to assess the efficacy and safety of gelatin tannate plus oral rehydration compared with oral rehydration alone. Methods We conducted a multicenter, parallel, randomized, controlled, single-blind, prospective, open-label trial. A central randomization center used computer generated tables to allocate treatments. The study was performed in two medical centers in Italy. Sixty patients 3–72 months of age with acute gastroenteritis were recruited (median age 18 months; age range 3–66 months): 29 received an oral rehydration solution (ORS) and 31 an ORS plus gelatin tannate (ORS ? G). The primary outcome was the number of bowel movements 48 and 72 h after initiating treatment. Secondary outcomes were: duration of diarrhea, stool characteristics and adverse events. Results No patient was lost at follow-up. No significant difference in the number of bowel movements after 48 h was reported (2.7 ± 1.3 ORS ? G; 3.2 ± 0.8 ORS; p = 0.06), although the ORS ? G group showed a significant improvement in stool consistency (3.7 ± 1.0 vs. 4.3 ± 0.8; p = 0.005). At 72 h, a significant reduction in bowel movements was reported in the ORS ? G group compared with the ORS group (1.0 ± 1.4 vs. 2.0 ± 1.7; p = 0.01). Mean duration of diarrhea was significantly lower in the ORS ? G group than in the ORS only group (76.8 ± 19.2 vs. 108 ± 24.0 h; p.0001). No adverse events were reported. Conclusions Gelatin tannate added to oral rehydration in children with acute diarrhea was associated with a significant decrease in bowel movements at 72 h, with an early improvement in the stool consistency and shorter disease duration

Changes in total choline concentration in the breast of healthy fertile young women in relation to menstrual cycle or use of oral contraceptives: a 3-T 1H-MRS study

BACKGROUND: To evaluate changes in total choline (tCho) absolute concentration ([tCho]) in the breast of healthy fertile women in relation to menstrual cycle (MC) or use of oral contraceptives (OC). METHODS: After institutional review board approval, we prospectively evaluated 40 healthy fertile volunteers: 20 with physiological MC, aged 28 ± 3 years (mean ± standard deviation; nOC group); 20 using OC, aged 26 ± 3 years (OC group). Hormonal assays and water-suppressed single-voxel 3-T proton magnetic resonance spectroscopy (1H-MRS) were performed on MC days 7, 14, and 21 in the nOC group and only on MC day 14 in the OC group. [tCho] was measured versus an external phantom. Mann-Whitney U test and Spearman coefficient were used; data are given as median and interquartile interval. RESULTS: All spectra had good quality. In the nOC group, [tCho] (mM) did not change significantly during MC: 0.8 (0.3-2.4) on day 7, 0.9 (0.4-1.2) on day 14, and 0.4 (0.2-0.8) on day 21 (p = 0.963). In the OC group, [tCho] was 0.7 (0.2-1.7) mM. The between-groups difference was not significant on all days (p ≥ 0.411). All hormones except prolactin changed during MC (p ≤ 0.024). In the OC group, [tCho] showed a borderline correlation with estradiol (r = 0.458, p = 0.056), but no correlation with other hormones (p ≥ 0.128). In the nOC group, [tCho] negatively correlated with prolactin (r = -0.587, p = 0.006) on day 7; positive correlation was found with estradiol on day 14 (r = 0.679, p = 0.001). CONCLUSIONS: A tCho peak can be detected in the normal mammary gland using 3-T 1H-MRS. The [tCho] in healthy volunteers was 0.4-0.9 mM, constant over the MC and independent of OC use

Paediatric HERMES: European accreditation of training centres in paediatric respiratory medicine

HERMES: European accreditation of training centres in paediatric respiratory medicine http://ow.ly/ZBmUg

Modifiable risk factors associated with bronchiolitis

Background: We sought to clarify possibly modifiable risk factors related to pollution responsible for acute bronchiolitis in hospitalized infants. Methods: For this observational study, we recruited 213 consecutive infants with bronchiolitis (cases: median age: 2 months; age range: 0.5-12 months; boys: 55.4%) and 213 children aged <3 years (controls: median age: 12 months; age range: 0.5-36 months; boys: 54.5%) with a negative medical history for lower respiratory tract diseases hospitalized at 'Sapienza' University Rome and IRCCS Bambino Gesù Hospital. Infants' parents completed a standardized 53-item questionnaire seeking information on social-demographic and clinical characteristics, indoor pollution, eating habits and outdoor air pollution. Multivariate logistic regression analyses were run to assess the independent effect of risk factors, accounting for confounders and effect modifiers. Results: In the 213 hospitalized infants the questionnaire identified the following risk factors for acute bronchiolitis: breastfeeding 3/43 months (OR: 2.1, 95% confidence interval [CI]: 1.2-3.6), presence of older siblings (OR: 2.8, 95% CI: 1.7-4.7), 3/44 cohabitants (OR: 1.5, 95% CI: 1.1-2.1), and using seed oil for cooking (OR: 1.7, 95% CI: 1.2-2.6). Having renovated their home in the past 12 months and concurrently being exposed daily to smoking, involving more than 11 cigarettes and two or more smoking cohabitants, were more frequent factors in cases than in controls (p = 0.021 and 0.05), whereas self-estimated proximity to road and traffic was similar in the two groups. Conclusions: We identified several risk factors for acute bronchiolitis related to indoor and outdoor pollution, including inhaling cooking oil fumes. Having this information would help public health authorities draw up effective preventive measures - for example, teach mothers to avoid handling their child when they have a cold and eliminate exposure to second-hand tobacco smoke

Severe pertussis infection in infants less than 6 months of age: clinical manifestations and molecular characterization

We conducted a study to determine the main traits of pertussis among unimmunized infants less than 6&nbsp;months of age. From August 2012 to March 2015, 141 nasopharyngeal aspirates (NPAs) were collected from infants with respiratory symptoms attending 2 major hospitals in Rome. Clinical data were recorded and analyzed. Lab-confirmation was performed by culture and realtime PCR. B. pertussis virulence-associated genes (ptxP, ptxA and prn), together with multilocus variable-number tandem repeat analysis (MLVA), were also investigated by the sequence-based analysis on the DNAs extracted from positive samples. Antibiotic susceptibility with Etest was defined on 18 viable B. pertussis isolates. Samples from 73 infants resulted positives for B. pertussis. The median age of the patients was 45&nbsp;d (range 7–165); 21 infants were treated with macrolides before hospital admission. Cough was reported for a median of 10&nbsp;d before admission and 18&nbsp;d after hospital discharge among infected infants, 84% of whom showed paroxysmal cough. No resistance to macrolides was detected. Molecular analysis identified MT27 as the predominant MLVA profile, combined with ptxP3-ptxA1-prn2 associated virulence genes. Although our data may not be generalized to the whole country, they provide evidence of disease severity among infants not vaccinated against pertussis. Moreover, genetically related B. pertussis strains, comprising allelic variants of virulence associated genes, were identified

Protection against pertussis in humans correlates to elevated serum antibodies and memory B cells

Pertussis is a respiratory infection caused by Bordetella pertussis that may be particularly severe and even lethal in the first months of life when infants are still too young to be vaccinated. Adults and adolescents experience mild symptoms and are the source of infection for neonates. Adoptive maternal immunity does not prevent pertussis in the neonate. We compared the specific immune response of mothers of neonates diagnosed with pertussis and mothers of control children. We show that women have pre-existing pertussis-specific antibodies and memory B cells and react against the infection with a recall response increasing the levels specific serum IgG, milk IgA, and the frequency of memory B cells of all isotypes. Thus, the maternal immune system is activated in response to pertussis and effectively prevents the disease indicating that the low levels of pre-formed serum antibodies are insufficient for protection. For this reason, memory B cells play a major role in the adult defense. The results of this study suggest that new strategies for vaccine design should aim at increasing long-lived plasma cells and their antibodies

Bronchiolitis. Analysis of 10 consecutive epidemic seasons

Bronchiolitis is the leading cause of hospitalization in infants under 12 months. Our aims were to analyze epidemiological characteristics of infants with bronchiolitis over 10 consecutive seasons and to evaluate whether there are any clinical differences between infants hospitalized for bronchiolitis during epidemic peak months and infants in non-peak months. We enrolled consecutive enrolled 723 previously healthy term infants hospitalized at the Paediatric Emergency Department, "Sapienza" University of Rome over the period 2004-2014. Fourteen respiratory viruses were detected from nasopharyngeal aspirates by molecular methods. Clinical and demographic data were extracted from clinical charts. Viruses were detected in 351 infants (48.5%): RSV in 234 (32.4%), RV in 44 (6.1%), hBoV in 11 (1.5%), hMPV in 12 (1.6%), co-infections in 39 (5.4%), and other viruses in 11 (1.5%). Analyzing the 10 epidemic seasons, we found higher incidence for bronchiolitis every 4 years with a peak during the months December-January. Infants hospitalized during peak months had lower family history for asthma (P = 0.003), more smoking mothers during pregnancy (P = 0.036), were slightly higher breastfed (0.056), had lower number of blood eosinophils (P = 0.015) and had a higher clinical severity score (P = 0.017). RSV was detected mostly during peak months, while RV was equally distributed during the seasons. We found some variations in bronchiolitis incidence during epidemics, and discriminative characteristics in infants hospitalized for bronchiolitis during peak months and in non-peak months, that might reflect two different populations of children. Pediatr Pulmonol. 2016; 9999:XX-XX. © 2016 Wiley Periodicals, Inc