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Objective: Osteoarthritis-related cartilage extracellular matrix remodeling is dependent on changes in chondrocyte protein expression. Yet, the role of ribosomes in chondrocyte translation regulation is un-known. In this exploratory study, we investigated ribosomal RNA (rRNA) epitranscriptomic-based ribo-some heterogeneity in human articular chondrocytes and its relevance for osteoarthritis.Methods: Sequencing-based rRNA 2'-O-methylation profiling analysis (RiboMethSeq) was performed on non-OA primary human articular chondrocytes (n = 5) exposed for 14 days to osteoarthritic synovial fluid (14 donors, pooled, 20% v/v). The SW1353 SNORD71 KO cell pool was generated using Lenti-CRISPRv2/Cas9. The mode of translation initiation and fidelity were determined by dual-luciferase re-porters. The cellular proteome was analyzed by LC-MS/MS and collagen type I protein expression was evaluated by immunoblotting. Loading of COL1A1 mRNA into polysomes was determined by sucrose gradient ultracentrifugation and fractionation.Results: We discovered that osteoarthritic synovial fluid instigates site-specific changes in the rRNA 2'-O-me profile of primary human articular chondrocytes. We identified five sites with differential 2'-O-me levels. The 2'-O-me status of 5.8S-U14 (one of identified differential 2'-O-me sites; decreased by 7.7%, 95% CI [0.9-14.5%]) was targeted by depleting the level of its guide snoRNA SNORD71 (50% decrease, 95% CI [33-64%]). This resulted in an altered ribosome translation modus (e.g., CrPV IRES, FC 3, 95% CI [2.2-4.1]) and promoted translation of COL1A1 mRNA which led to increased levels of COL1A1 protein (FC 1.7, 95% CI [1.3-2.0]).Conclusions: Our data identify a novel concept suggesting that articular chondrocytes employ rRNA epitranscriptomic mechanisms in osteoarthritis development.(c) 2023 The Authors. Published by Elsevier Ltd on behalf of Osteoarthritis Research Society International. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

In plant cells, a large pool of iron (Fe) is contained in the nucleolus, together with that in chloroplasts and mitochondria. A central determinant for intracellular distribution of Fe is nicotianamine (NA) generated by nicotianamine synthase (NAS). Here, we characterized Arabidopsis thaliana plants with disrupted NAS genes to modify accumulation of nucleolar iron and understand its role in nucleolar functions and more specifically in rRNA gene expression. We found that nas124 triple mutant plants, which contain lower quantities of the iron ligand NA, also contain less iron in the nucleolus. This is concurrent with the expression of normally silenced rRNA genes from Nucleolar Organizer Regions 2 (NOR2). Notably, in nas234 triple mutant plants, which also contain lower quantities of NA, nucleolar iron and rDNA expression are not affected. In contrast, in both nas124 and nas234, specific RNA modifications are differentially regulated in a genotype dependent manner. Taken together the data point out the impact of specific NAS activities in RNA gene expression. We discuss the interplay between NA and nucleolar iron with rDNA functional organization and RNA methylation.

Resume Le cancer de l’ovaire est le cinquieme cancer chez la femme en France avec 4714 nouveaux cas en 2017. Plus de 70 % des patientes dont la maladie est initialement localement evoluee vont etre atteints d’une recidive locoregionale ou a distance. Les options therapeutiques dans cette situation ne sont pas consensuelles. Elles reposent sur une chimiotherapie, associee eventuellement a une chirurgie de cytoreduction iterative lorsqu’elle est supportable par la patiente. La place de la radiotherapie dans la prise en charge de la maladie est occultee dans la tres grande majorite des referentiels nationaux ou internationaux. Nous avons realise une revue generale de la litterature afin de preciser la place de l’irradiation dans la prise en charge globale des cancers ovariens, notamment en situation de recidive.

Background Few risk factors are associated with the risk of relapses of Crohn’s disease in children. Aims The aims of this retrospective cohort study were to describe the rate of relapses in children with Crohn’s disease, its evolution over the past decade and to determine risk factors associated with relapse. Methods Patients under 18 years old and diagnosed between 2009 and 2019 were included. Patients clinical, endoscopic, histological, and laboratory characteristics, as well as their treatments, where collected from their medical records and the prospective CHU Sainte-Justine inflammatory bowel disease registry. Survival analyses and Cox regression models were used to assess the impact of those risk factors on relapse. Results 639 patients were included. There was a decrease in the clinical relapse rate over the past decade: 70.9% of patients diagnosed between 2009 and 2014 experienced a relapse compared to 49.1% of patients diagnosed between 2015 and 2019 (p Conclusions Relapse risk was significantly associated with baseline clinical, endoscopic, histological and laboratory data and treatment strategies. These results could help better select treatment options for pediatric Crohn’s disease at induction and maintenance. Kaplan-Meier curve representing patients time to relapse according to the mean infliximab level in post-induction. Funding Agencies NoneFonds Recherche Santé Québec / Fondation du CHU Sainte-Justine

Background The natural evolution of Crohn’s disease is incompletely understood in the pediatric population. Data on factors influencing time-to-remission are very limited in the literature. Aims The aim of this retrospective cohort study was to describe the time to clinical remission in children with Crohn’s disease as well as changes over the past decade and to identify factors associated with time to clinical remission. Methods Patients under 18 years old diagnosed between 2009 and 2019 were included. All data were collected from the patients’ medical records and the CHU Sainte-Justine inflammatory bowel disease registry. Survival analyses and linear regression models were used to assess the impact of clinical, laboratory, endoscopic, histological and therapeutic factors on time to clinical remission. Results 654 patients were included in the study. There was no change in the time to clinical remission over the past decade. Female sex in adolescents (ajusted bêta regression coefficient (aβ)= 31.8 days, p= 0.02), upper digestive tract involvement (aβ= 46.4 days, p= 0.04), perianal disease (aβ= 32.2 days, p= 0.04), presence of active inflammation on biopsies (aβ= 46.7 days, p= 0.01) and oral 5-ASA exposure (aβ=56.6 days, p= 0.002) were all associated with longer time to clinical remission. However, antibiotic exposure (aβ= -29.3 days, p=0.04), increased eosinophils on biopsies (aβ= -29.6 days, p=0.008) and combination of exclusive enteral nutrition and TNF- alpha inhibitors as induction therapy (aβ= -36.8, p=0.04) were associated with shorter time to clinical remission. Conclusions Time to clinical remission did not improve during the decade and was associated with baseline clinical and histological data and treatment strategies. Combination of enteral nutrition and TNF-alpha inhibitors was associated with faster clinical remission. Kaplan-Meier curve representing the time to clinical remission of patients according to the first induction treatment administered. Funding Agencies NoneFonds Recherche Santé Québec / Fondation du CHU Sainte-Justine

Background Crohn’s disease (CD) triggers are incompletely understood and the incidence of the disease has been increasing. Aims The aims of this study were to describe the trends in the clinical, endoscopic, histological, and laboratory characteristics of pediatric CD during the last decade and to describe the seasonal variation of disease presentation at diagnosis. Methods Patients under 18 years old and diagnosed between 2009 and 2019 were included. Patients clinical, endoscopic, histological, and laboratory data were collected from the medical records. Data were analyzed for the cohort as a whole and according to diagnostic periods (2009–2014 and 2015–2019) and seasons. Results 654 patients were included in the study. The total number of incident CD cases significantly increased yearly. Patients diagnosed between 2015 and 2019 were younger at diagnosis (OR: 2.30, p There were fewer CD diagnosis during winter. The highest vitamin D levels in patients occurred in summer and fall, but the majority of patients had, regardless of the season of diagnosis, severe vitamin D deficiency (the median vitamin D level was 60.0 nmol/L in summer and fall compared to 47.0 nmol/L in winter-spring, p=0.003). Vitamin D levels at diagnosis are inversely correlated with PCDAI (Pearson correlation coefficient = -0.19, p=0.03) and SES-CD (-0.20, p=0.04). Patients diagnosed in fall had lower PCDAI and SES-CD scores, less failure to thrive, less digestive symptoms and less extensive digestive involvement. Colonic disease was significantly more frequent during summer and fall (27.3% of patients diagnosed in summer and fall versus 18.2% of cases in winter and spring, p=0.01). Conclusions The disease phenotype has changed over the years and there are important seasonal trends in the frequency and severety of the disease suggesting possible disease triggers. Our findings provide interesting avenues for future research, such as identifying the clinical significance of granulomas, vitamin D deficiency and microbiota on pediatric CD activity. PCDAI at diagnosis according to the season. Funding Agencies NoneFonds Recherche Santé Québec / Fondation du CHU Sainte-Justine

Background Crohn’s disease (CD) triggers are incompletely understood and the incidence of the disease has been increasing. The aims of this study were to describe the trends in the clinical, endoscopic, histological, and laboratory characteristics of pediatric CD during the last decade and to describe the seasonal variation of disease presentation at diagnosis. Methods Patients under 18 years old and diagnosed between 2009 and 2019 were included. Patients clinical, endoscopic, histological, and laboratory data were collected from the medical records. Data were analyzed for the cohort as a whole and according to diagnostic periods (2009–2014 and 2015–2019) and seasons. Results 654 patients were included in the study. The total number of incident CD cases significantly increased yearly. Patients diagnosed between 2015 and 2019 were younger at diagnosis (OR: 2.30, p There were fewer CD diagnosis during winter. The highest vitamin D levels in patients occurred in summer and fall, but the majority of patients had, regardless of the season of diagnosis, severe vitamin D deficiency (the median vitamin D level was 60.0 nmol/L in summer and fall compared to 47.0 nmol/L in winter-spring, p=0.003). Vitamin D levels at diagnosis are inversely correlated with PCDAI (Pearson correlation coefficient = -0.19, p=0.03) and SES-CD (-0.20, p=0.04). Patients diagnosed in fall had lower PCDAI and SES-CD scores, less failure to thrive, less digestive symptoms and less extensive digestive involvement. Colonic disease was significantly more frequent during summer and fall (27.3% of patients diagnosed in summer and fall versus 18.2% of cases in winter and spring, p=0.01). Figure 1:PCDAI at diagnosis according to the season. Figure 2:Proportion of patients with L1-L2-L3 disease locations by the Paris classification according to the season of diagnosis. Conclusion The disease phenotype has changed over the years and there are important seasonal trends in the frequency and severety of the disease suggesting possible disease triggers. Our findings provide interesting avenues for future research, such as identifying the clinical significance of granulomas, vitamin D deficiency and microbiota on pediatric CD activity.

Background The natural evolution of Crohn’s disease is incompletely understood in the pediatric population. Data on factors influencing time-to-remission are very limited in the literature. The aim of this retrospective cohort study was to describe the time to clinical remission in children with Crohn’s disease as well as changes over the past decade and to identify factors associated with time to clinical remission. Methods Patients under 18 years old diagnosed between 2009 and 2019 were included. All data were collected from the patients’ medical records and the CHU Sainte-Justine inflammatory bowel disease registry. Survival analyses and linear regression models were used to assess the impact of clinical, laboratory, endoscopic, histological and therapeutic factors on time to clinical remission. Results 654 patients were included in the study. There was no change in the time to clinical remission over the past decade. Female sex in adolescents (ajusted bêta regression coefficient (aβ)= 31.8 days, p= 0.02), upper digestive tract involvement (aβ= 46.4 days, p= 0.04), perianal disease (aβ= 32.2 days, p= 0.04), presence of active inflammation on biopsies (aβ= 46.7 days, p= 0.01) and oral 5-ASA exposure (aβ=56.6 days, p= 0.002) were all associated with longer time to clinical remission. However, antibiotic exposure (aβ= -29.3 days, p=0.04), increased eosinophils on biopsies (aβ= -29.6 days, p=0.008) and combination of exclusive enteral nutrition and TNF- alpha inhibitors as induction therapy (aβ= -36.8, p=0.04) were associated with shorter time to clinical remission. Figure 1: Kaplan-Meier curve representing time to clinical remission in patients 13 years old and older by sex. Figure 2: Kaplan-Meier curve representing the time to clinical remission of patients according to the first induction treatment administered. Conclusion Time to clinical remission did not improve during the decade and was associated with baseline clinical and histological data and treatment strategies. Combination of enteral nutrition and TNF-alpha inhibitors was associated with faster clinical remission.

Background Few risk factors are associated with the risk of relapses of Crohn’s disease in children. The aims of this retrospective cohort study were to describe the rate of relapses in children with Crohn’s disease, its evolution over the past decade and to determine risk factors associated with relapse. Methods Patients under 18 years old and diagnosed between 2009 and 2019 were included. Patients clinical, endoscopic, histological, and laboratory characteristics, as well as their treatments, where collected from their medical records and the prospective CHU Sainte-Justine inflammatory bowel disease registry. Survival analyses and Cox regression models were used to assess the impact of those risk factors on relapse. Results 639 patients were included. There was a decrease in the clinical relapse rate over the past decade: 70.9% of patients diagnosed between 2009 and 2014 experienced a relapse compared to 49.1% of patients diagnosed between 2015 and 2019 (p Figure 1: Kaplan-Meier curve representing patients time to relapse according to the first maintenance treatment administered. Conclusion Relapse risk was significantly associated with baseline clinical, endoscopic, histological and laboratory data and treatment strategies. These results could help better select treatment options for pediatric Crohn’s disease at induction and maintenance. Figure 2: Kaplan-Meier curve representing patients time to relapse according to the mean infliximab level in post-induction.

Ovarian cancer is the fifth most common cancer in women in France with 4714 new cases in 2017. More than 70% of patients whose disease is initially locally advanced will present locoregional or distant recurrence. Therapeutic options in this situation are not consensual. They are based on chemotherapy possibly associated with an iterative cytoreductive surgery when it is bearable by the patient. The place of radiotherapy in the management of the disease is hidden in the vast majority of national or international standards. We conducted a general review of the literature to clarify the role of irradiation in the global management of ovarian cancers, particularly in recurrence.

BACKGROUND: Digestive adenocarcinoma is rare in the pediatric population with only a few case reports in the literature. AIMS: We describe 2 pediatric patients with digestive adenocarcinoma, one in the colon and the other in the stomach, diagnosed in St Justine University Hospital Center in 2018. METHODS: Case 1: A fourteen-year-old girl presented with severe abdominal pain. She had a 3-month history of diarrhea, rectal bleeding and weight-loss. She had a morbid obesity with a BMI at 41.8 kg/m(2). There was no family history of malignancy. Colonoscopy revealed an exophytic, friable and hemorrhagic mass at the recto sigmoidal junction. Histopathology showed an infiltrating poorly differentiated adenocarcinoma with p53 mutation. Chemotherapy was initiated. One month later, repeat work-up showed progression of the recto-sigmoidal mass with stenosis of the colic lumen, as well as a new stenotic zone upstream. There was also progression of the peritoneal carcinomatosis. The clinical course was marked by pulmonary embolism and repeated intestinal occlusive episodes. Case 2: A 13-year-old boy presented with a 3 week history of severe epigastric pain, hematemesis, breathlessness and asthenia. He reported a 6-month history of dysphagia, anorexia, nausea and a 5 kg weight loss. Family’s medical history revealed a paternal grandfather with colon cancer and a cousin with sarcoma. Gastroscopy showed a mass at the gastroesophageal junction. Histopathology showed a moderately differentiated high-grade adenocarcinoma with p53 gene mutation. Despite 2 months of chemotherapy, there was no regression of the lesions and the patient required nasogastric feedings. He also had deep vein thrombosis. RESULTS: In those 2 pediatric cases, the digestive symptoms were non-specific. Tumors were visible at endoscopy and biopsy could be performed. At the time of diagnosis, adenocarcinomas were already metastatic and carried a poor prognosis. Both patients had high serum levels of Carcinoembryonic Antigen (CEA), respectively 706.9 and 864.7 μg/L. CONCLUSIONS: Adenocarcinomas are extremely rare in children. They are generally aggressive and have a poor prognosis. Pediatric gastroenterologists must consider this entity in their differential diagnosis of digestive symptoms. A rigorous and comprehensive approach must be taken. The CEA blood test is useful for detecting recurrent colorectal cancer but would not be useful as a screening tool in the pediatric population. FUNDING AGENCIES: None

Objectif de l’etude Nous avons revu les donnees cliniques et dosimetriques de nos premiers patients traites avec modulation d’intensite sur HalcyonTM pour un carcinome mammaire localise ou localement avance. Materiel et methode Trente patientes ont ete prises en charge dans notre centre pour un carcinome mammaire localise (n = 21) ou localement evolue (n = 9). L’âge median etait de 67,5 ans. La lateralite de l’irradiation etait droite (n = 14), gauche (n = 16). Le traitement a ete realise avec modulation d’intensite en utilisant des photons 6 MV sans filtre compensateur (FFF) sur HalcyonTM (Varian) soit en arctherapie ou en radiotherapie conformationnelle avec modulation d’intensite (RCMI) par faisceaux dynamiques modules ou technique hybride RCMI/arctherapie. La planification dosimetrique a ete effectuee sur Eclipse v15.5. Le repositionnement a ete realise par imagerie planaire de haute energie ou conique de haute energie, dont la contribution de dose a ete incluse dans parametres dosimetriques. Resultats Le temps d’irradiation moyen etait de 50 s. La toxicite aigue a ete marquee par une radiodermite de grade 1 (n = 24) ou 2 (n = 6), une œsophagite de grade 1 (n = 5). Pour les cancers du sein localises, les volumes medians pulmonaires homolateraux V20 Gy, V5 Gy (V × Gy : volume recevant × Gy) etaient respectivement de 8,8 % [1,8–15 %], 24 % [14–28,8 %]. Les doses moyennes medianes dans le poumon homolateral et le cœur etaient respectivement de 6,36 Gy [3,8–8,3 Gy] et 1,9 Gy [1–4,2 Gy]. Pour les cancers du sein localement evolues, les volumes medians pulmonaires homolateraux V20 Gy, V5 Gy etaient respectivement de 22 % [7,5–28 %] et 66 % [22,8–89 %]. Les doses moyennes medianes dans le poumon homolateral et au cœur etaient respectivement de 12,5 Gy [5,9–15,4 Gy] et 1,9 Gy [1,3–6,2 Gy]. Conclusion La radiotherapie avec modulation d’intensite des carcinomes mammaires sous HalcyonTM permet d’obtenir un gain dosimetrique et de temps d’irradiation comparativement aux techniques classiques, notamment pour des balistiques complexes sans augmenter la toxicite aigue precoce. La comptabilisation de la dose delivree par l’imagerie dans les parametres dosimetriques finaux semble un atout.

BACKGROUND: Percutaneous gastrostomy (PEG) has become a key element in managing children with nutrition or feeding issues. Reversal of malnutrition shortly after gastrostomy has been shown in many pediatric studies, however literature on maintenance of nutritional status following initial catch-up growth is limited. AIMS: To analyze the long-term follow-up of children with PEG in terms of nutritional outcomes as defined by improvement in weight-for-height z scores. To review the procedure-related complication rates specific to our center. METHODS: This is a retrospective review of all PEG procedures performed at our tertiary Children’s Hospital from 1999 to 2015. All PEGs were placed by the same team of pediatric gastroenterologists using the standard pull technique. Prophylactic antibiotics were given for 24h. Nutritional outcomes were evaluated by comparing the weight-for-height z scores (CDC growth charts) at the time of tube placement and either at the time of last follow-up for children receiving gastrostomy feeding, or at the time of tube removal, fundoplication or death. PEG-related complications were recorded. RESULTS: In the 256 patients who underwent successful PEG placement, diagnoses were as follow: neuromuscular disease (n=136, 53%), cystic fibrosis (n=30, 12%), metabolic disease (n=18, 7%), chromosomal abnormalities/genetic syndromes (n=18, 7%), nonorganic failure to thrive (n=39, 15%) and other (n=15, 6%). Median age at the time of PEG placement was 3.9 years (0.4–19.9 years) and median follow-up duration was 3.2 years (0–16 years). Significant improvement in weight-for-heigth z score was reported for all subgroups except for the “metabolic disease” and “other” subgroups: neuromuscular disease (△=0.62, P=0.0008), cystic fibrosis (△=0.8, P=0.004), metabolic disease (△=0.37, P=0.4), chromosomal abnormalities/genetic syndromes (△=1.01, P=0.01), nonorganic failure to thrive (△=0.7, P=0.005). A total of 61 complications were reported: 35 cellulitis including 17 requiring intravenous antibiotics, 16 accidental dislodgements, 7 buried bumper syndromes, and 2 perforations. A total of 123 patients had known reflux prior to PEG placement, while 39 (32%) had resolution of symptoms, 84 (68%) had persistent reflux with 18 requiring fundoplicature. CONCLUSIONS: Our study illustrates that improvement in nutritional status following PEG is maintained during the long term, reinforcing the benefits of gastrostomy feeding when enteral nutrition is required. PEG is a safe method to provide enteral feeding in children. Future studies defining preoperative clinical factors to help clinicians to predict which patient populations are at higher risk of poor nutritional rehabilitation, complications or need for anti-reflux surgery are needed. FUNDING AGENCIES: None

Resume Introduction et but de l’etude Les modalites de guidage par imagerie de la radiotherapie mammaire ne sont pas consensuelles. Nous avons evalue nos pratiques et l’influence des changements morphologiques du sein pendant la radiotherapie sur Halcyon™. Materiel et methodes Parmi plus de 1000 patientes traitees, 128 dossiers ont ete tires au sort et analyses retrospectivement. Il s’agissait d’une radiotherapie conformationnelle avec modulation d’intensite (RCMI, n = 104) ou d’une arctherapie volumetrique avec modulation d’intensite (n = 24) en utilisant respectivement trois a quatre faisceaux modules ou trois a cinq arcs partiels de photons de 6 MV en mode sans egalisateur de filtre (flattening filter-free, FFF). L’optimisation dosimetrique utilisait un bolus virtuel de 1,5 cm en arctherapie volumetrique modulee ou une extension de fluence (skin flash) de 1,5 cm en RCMI afin de tenir compte notamment des mouvements respiratoires. Avant chaque seance, une tomographie conique de basse ou de haute energie a ete realisee. Une scanographie dosimetrique a ete effectuee avant et a mi-parcours du traitement, voire plus precocement selon les modifications anatomiques. Les changements morphologiques etaient notes et rapportes aux medecins, physiciens par les manipulateurs d’electroradiologie medicale. Le cas echeant, un recalage semiautomatique rigide suivi d’une deformation elastique et verification medicale des contours etaient realises. En cas de modification majeure, une nouvelle dosimetrie etait recalculee. Resultats et analyse statistique Chez 22 patientes il y a eu une modification morphologique, avec un œdeme radio-induit (n = 6), une diminution de lymphocele/œdeme (n = 16). Hormis les difficultes de repositionnement, les modifications anatomiques induisaient un impact dosimetrique faible sur la couverture de la glande mammaire avec des zones de surdosage ou de sous-dosage des volumes cibles du sein/de la paroi de moins de 3 % (doses maximales, moyennes et minimales). L’impact dosimetrique sur les aires ganglionnaires et les organes a risque etait negligeable. Conclusion Cette etude valide nos pratiques de controle quotidienne par tomographie conique et confirme la robustesse de nos techniques d’optimisation dosimetrique. Une etude est en cours pour confirmer ces resultats et estimer precisement l’impact dosimetrique quotidien a partir de la tomographie conique ainsi que l’apport du repositionnement surfacique.

The goal of this work was to evaluate the potential benefit of deep inspiration breath-hold (DIBH) compared to free breathing (FB) radiotherapy in a homogeneous population of patients with lung cancer.A total of 25 patients with non-small cell lung cancer treated by DIBH underwent an additional FB CT scan. The DIBH and FB treatment plans were compared. Target volume was compared using coverage, homogeneity, and conformal indices. Organs at risk were compared using V(5), V(13), V(20), V(25), V(37), mean dose (D(mean)) for lungs, V(40) and D(mean) for the heart, V(50), D(mean) and maximum dose (D(max)) for the esophagus, and using biological indices, i.e., the equivalent uniform dose (EUD) and the normal tissue complication probability (NTCP).Median age was 62 years. Prescribed total dose was 66 Gy. Conformity index was improved with DIBH (0.67 vs. 0.58, p = 0.046) but coverage and homogeneity indices were not significantly different. Lung dosimetric parameters were improved using DIBH: D(mean) (13 vs. 15 Gy, p = 10(-4)), V(5) (43 vs. 51%, p = 6.10(-5)), V(13) (31 vs. 38%, p = 2.10(-3)), V(20) (25 vs. 31%, p = 0.01), V(25) (22% vs. 27%, p = 0.01) and V(37) (12 vs. 16%, p = 0.03), EUD (8.2 vs. 9.9 Gy, p = 3.10(-4)), and NTCP (1.9 vs. 4.8%, p = 10(-3)). For the heart, D(mean) (14 vs. 17 Gy, p = 0.003), V(40) (12 vs. 17%, p = 0.004), and EUD (19 vs. 22 Gy, p = 6.10(-4)) were reduced with DIBH, whereas V(30) and NTCP were similar. DIBH improved the D(mean) (28 vs. 30 Gy, p = 0.007) and V(50) (25 vs. 30%, p = 0.003) for the esophagus, while EUD, NTCP, and D(max) were not altered.DIBH improves the target conformity index and heart and lung dosimetry in lung cancer patients treated with radiotherapy. The clinical implications of these findings should be confirmed.

Resume Objectif de l’etude L’indication d’une radiotherapie externe est parfois posee chez des patients porteurs d’un stimulateur cardiaque. Ce traitement peut occasionner des dysfonctionnements lies soit a l’effet ionisant des rayons, soit a des interferences electromagnetiques. Nous avons repris le cas de patientes atteintes d’un cancer du sein traitees par une irradiation mammaire ou parietale, parfois aussi des aires ganglionnaires de drainage, pour evaluer la tolerance et les repercussions de la radiotherapie par rapport au stimulateur cardiaque. Patientes et methodes Plus de 900 patientes ont ete traitees par irradiation externe pour un cancer du sein de novembre 2008 a decembre 2009 dans notre departement par un accelerateur lineaire de haute energie (par photons X de 4 a 6 MV et electrons). Parmi ces dernieres, sept etaient porteuses d’un stimulateur cardiaque. Toutes les patientes ont ete irradiees dans le sein, la paroi thoracique ou les aires ganglionnaires. La dose totale prescrite etait de 50 Gy en 25 fractions dans le sein ou la paroi thoracique et de 46 Gy en 23 fractions dans les aires ganglionnaires. Un boost de 16 Gy en huit fractions etait indique chez certaines patientes traitees par chirurgie conservatrice. Le rythme cardiaque de toutes les patientes etait monitore pendant les seances et surveille par un medecin oncologue radiotherapeute. Tous les stimulateurs cardiaques ont ete controles par le cardiologue des patientes avant et apres l’irradiation. Resultats Sept patientes ont ete adressees dans notre departement pour radiotherapie postoperatoire dans le cadre d’un cancer du sein. Parmi ces sept patientes, seule une finalement s’est vue recuser la radiotherapie et a beneficie d’une mastectomie. Dans quatre cas, le stimulateur cardiaque a ete repositionne avant le debut de la radiotherapie. Six patientes âgees de 48 a 84 ans ont ete traitees par irradiation pour leur cancer du sein. Quatre patientes ont ete traitees par chirurgie conservatrice suivie d’une irradiation mammaire et deux par mastectomie suivie d’une irradiation de la paroi thoracique et des aires ganglionnaires sus- et sous-claviculaire et mammaire interne. La dose au stimulateur cardiaque a ete calculee et etait toujours inferieure a 2 Gy. Il n’a ete observe aucun dysfonctionnement des stimulateurs cardiaques pendant la radiotherapie. Conclusion La prise en charge multidisciplinaire incluant un eventuel changement de positionnement du stimulateur cardiaque avant radiotherapie et le monitoring quotidien ont permis le deroulement sans incident de la radiotherapie pour nos patientes. Il est neanmoins necessaire de mettre a jour des recommandations precisant la dose maximale tolerable aux differents constituants du stimulateur cardiaque.

Resume Objectifs Le but de cette etude est de rapporter la tolerance et la reponse de l’association concomitante de radiotherapie a l’ensemble de l’encephale et de trastuzumab pour des metastases encephaliques de cancer du sein. Patientes et methodes Nous avons realise une etude retrospective de 31 patientes irradiees pour metastases cerebrales d’un cancer du sein avec surexpression Her2 et qui ont recu une irradiation cerebrale en association concomitante avec le trastuzumab. La dose delivree etait de 30 Gy en dix fractions dans la majorite des cas. Toutes les patientes ont beneficie d’un suivi hebdomadaire afin d’evaluer la tolerance. Toutes les patientes ont poursuivi le trastuzumab apres la radiotherapie. Resultats L’âge moyen au moment du diagnostic de la metastase cerebrale etait de 55 ans (38 a 73 ans) avec un etat general conserve ( performance status selon OMS : 0-2). Le delai median avant la progression etait de 10,5 mois. L’evolution clinique etait marquee par une reponse chez 27 patientes (87,1 %) avec, pour 23 d’entre elles, une disparition complete des symptomes (74,2 %). Une remission radiologique complete etait notee chez six patientes (19,4 %), et partielle chez 17 (54,8 %). Le traitement a ete bien tolere, seules sept patientes (23 %) ont presente des nausees grades 1 et 2, une asthenie ou des cephalees. Conclusion Nos resultats suggerent que la poursuite du trastuzumab pendant la radiotherapie des metastases cerebrales est bien toleree. Le taux de reponse est encourageant mais il est necessaire d’evaluer ces resultats par des etudes prospectives comparant la radiotherapie seule a l’association radiotherapie-trastuzumab.

Helical tomotherapy (HT), an image-guided, intensity-modulated, radiation therapy technique, allows for precise targeting while sparing normal tissues. We retrospectively assessed the feasibility and tolerance of the hepatobiliary HT in 9 patients. A total dose of 54 to 60 Gy was prescribed (1.8 or 2 Gy per fraction) with concurrent capecitabine for 7 patients. There were 1 hepatocarcinoma, 3 cholangiocarcinoma, 4 liver metastatic patients, and 1 pancreatic adenocarcinoma. All but one patient received previous therapies (chemotherapy, liver radiofrequency, and/or surgery). The median doses delivered to the normal liver and to the right kidney were 15.7 Gy and 4.4 Gy, respectively, below the recommended limits for all patients. Most of the treatment-related adverse events were transient and mild in severity. With a median followup of 12 months, no significant late toxicity was noted. Our results suggested that HT could be safely incorporated into the multidisciplinary treatment of hepatobiliary or pancreatic malignant disease.

Purpose To determine prospectively intermediate-term toxicity and quality of life (QoL) of prostate cancer patients after intensity-modulated radiotherapy (IMRT). Patients and Methods Fifty-five patients with localized prostate adenocarcinoma were treated by IMRT (76 Gy). Physicians scored acute and late toxicity using the Common Terminology Criteria for Adverse Events version 3.0. Patients assessed general and prostate-specific QoL before IMRT (baseline) and at 2, 6, and 18 months using European Organization for Research and Treatment of Cancer questionnaires QLQ-C30(+3) and QLQ-PR25. Results Median age was 73 years (range, 54–80 years). Risk categories were 18% low risk, 60% intermediate risk, and 22% high risk; 45% of patients received hormonal therapy (median duration, 6 months). The incidence of urinary and bowel toxicity immediately after IMRT was, respectively, 38% and 13% (Grade 2) and 2% and none (Grade 3); at 18 months it was 15% and 11% (Grade 2) and none (Grade 3). Significant worsening of QoL was reported at 2 months with regard to fatigue (+11.31, p = 1.10 −7 ), urinary symptoms (+9.07, p = 3.10 −11 ), dyspnea (+7.27, p = 0.008), and emotional (−7.02, p = 0.002), social (−6.36, p = 0.003), cognitive (−4.85, p = 0.004), and physical (−3.39, p = 0.007) functioning. Only fatigue (+5.86, p = 0.003) and urinary symptoms (+5.86, p = 0.0004) had not improved by 6 months. By 18 months all QoL scores except those for dyspnea (+8.02, p = 0.01) and treatment-related symptoms (+4.24, p = 0.01) had returned to baseline. These adverse effects were exacerbated by hormonal therapy. Conclusion High-dose IMRT with accurate positioning induces only a temporary worsening of QoL.

The radiation dose received by the eye depends on the pathology, tumour location (ocular globe, orbit, neighboring structures) and the radiation technique. The major complication is the complete loss of vision, which is often multifactorial. This article, based on a literature review, describes the radiation effects and the tolerance doses for all eye structures: cornea, lens, retina, optic nerves, orbit and ocular adnexa.

In Howells's distinctive vision of the social world, there is something inimitable about upper- bourgeois culture—something that defies the aspirants' attempts to acquire or fake upper-class behaviors. In The Rise of Silas Lapham, he dramatizes for readers what none of his characters can articulate but all of them finally “feel,” namely the “fine yet impassable” differences between classes.

Resume Objectif de l’etude Malgre une augmentation recente du nombre des internes en oncologie–radiotherapie ces dix dernieres annees, l’evolution globale de la demographie des oncologues radiotherapeutes reste tres inferieure aux besoins lies aux departs a la retraite et a l’evolution de la discipline. Materiel et methodes Lors des cours nationaux annuels organises par la Societe francaise des jeunes radiotherapeutes oncologues (SFJRO), la Societe francaise de radiotherapie oncologique (SFRO) et le College national des enseignants de cancerologie (Cnec) et soutenus par l’Institut national du cancer (Inca), differentes enquetes ont ete realisees. Resultats Depuis 2002, le nombre total des internes en formation dans l’option oncologie–radiotherapie a augmente regulierement (50, 75, 103 et 109 internes respectivement en 2000, 2005, 2007 et 2008). Il y a legerement plus de femmes que d’hommes (51,5 % contre 48,5 %). L’enseignement a ete evalue a l’aide d’une echelle visuelle analogique et le score etait de 56 pour la formation pratique et 61 pour la formation theorique. Les internes ont pu beneficier d’autres types de formation (analyse de cas cliniques, seances de bibliographie) dans certaines universites. L’analyse des motivations du choix de la specialite oncologie–radiotherapie, a montre un interet commun a la fois pour la pratique medicale et les aspects techniques. Les notions d’innovation, de technologie, d’imagerie et de recherche apparaissaient aussi clairement. Seize internes finissent leur formation fin 2008, 42 en 2009 et 27 en 2010. Presque tous les internes pensent qu’un « post-internat » est necessaire pour completer la formation en tant que chef de clinique – assistant (CCA). Cependant, seuls 36 postes de CCA sont disponibles en France, soit la moitie des besoins. Seulement 21 internes sur 104 sont assures d’avoir un poste de CCA et la disponibilite de ce type de poste reste incertaine pour les autres. Conclusions Malgre des creations recentes de postes de CCA dans le cadre du plan cancer, de dix a 20 postes supplementaires sont necessaires pour que tous les internes puissent y acceder et qu’ils beneficient d’une formation de qualite dans cette discipline transversale, medicale et technique.

Contexte L’ustekinumab est un anticorps monoclonal dirige contre la sous-unite p40 de l’interleukine-12/23. Il a ete montre superieur au placebo dans l’induction de la reponse et le maintien de la remission chez les patients adultes atteints de maladie de Crohn moderee a severe, mais pas encore etudie en pediatrie. Buts de l’etude Decrire la securite et l’efficacite de l’ustekinumab chez les enfants atteints de maladie de Crohn refractaire. Methodes Nous rapportons six patients (4 garcons) qui ont recu de l’ustekinumab dans notre centre entre fevrier et octobre 2014 pour maladie de Crohn refractaire aux anti-TNF. Resultats L’âge median au debut de l’ustekinumab etait de 16,4 ans (10,7–18,2) et la duree mediane de la maladie etait de 3,6 ans (1,0–8,4). La localisation de la maladie distale selon la classification de Paris etait L1 chez 1 patient, L3 chez 4 et pas atteinte colique chez 1 ; la localisation haute etait : L4a chez 2 patients et L4b chez 2. Le phenotype etait non penetrant non stenosant dans 5 cas et stenosant dans 1. Aucun patient n’avait de maladie perianale. Tous les patients avaient echoue ou etaient intolerants aux immunomodulateurs (5 patients a l’azathioprine, 6 au methotrexate). Tous avaient eu un echec d’infliximab (2 avaient interrompu pour perte de reponse, 2 pour allergies ou evenements indesirables et 2 pour les deux raisons). Cinq patients avaient echoue a l’adalimumab, et un n’en avait pas recu. Un patient avait eu deux resections intestinales avec stricturoplasties. A l’initiation de l’ustekinumab, quatre patients etaient sous prednisone et 3 sous methotrexate. L’ustekinumab etait administree par voie sous-cutanee a la dose de 45 mg (si le poids ≤ 45 kg) par semaine ou 90 mg (si le poids > 45 kg) par semaine, pendant trois semaines pendant le traitement d’induction. Apres le traitement d’induction, 3 patients ont eu une reponse clinique, 1 etait en remission clinique et 2 n’ont pas eu de reponse. Cinq patients ont continue le traitement d’entretien de 45 mg toutes les 8 semaines ou 90 mg toutes les 8 semaines en fonction de la posologie recue lors de l’induction. Une augmentation de la dose etait necessaire dans deux cas. Au total, les patients ont recu une mediane de 6,5 doses (3–9) d’ustekinumab. La reponse au traitement d’entretien a ete evaluee apres une periode mediane de 5,1 mois (3,7 a 7,1) : 1 patient etait en remission clinique, 2 avaient une reponse clinique et 2 n’ont eu aucune reponse, dont l’un a necessite une colectomie subtotale avec ileostomie. Aucun evenement indesirable n’a ete note. Conclusions L’ustekinumab est bien tolere chez les patients pediatriques. Plus de donnees sont necessaires pour confirmer l’efficacite montree chez l’adulte.

T^he consensus among several generations of critics is that Wharton's 1907 novel The Fruit of the Tree lacks a stable core of concerns.1 "There was stuff here for a dozen novels," Millicent Bell concludes (253-54). Henry James's judg ment was no less decisive for his characteristic indirection. After praising the novel to Wharton as a thing "of a great deal of (though not perhaps of a completely superior) art," he adds, "Where my qualifications would come in would be as to the terrible question of the com position 8t conduct of the thing" (Powers 78). He would later complain to Mary Cadwalader Jones of the novel s "strangely infirm composi tion and construction?as if she hadn't taken

Enteral feeding, the provision of liquid nutrients into the gastrointestinal tract, is an important component of pediatric care. For the infant or child with a functioning or even a partially-functioning GI tract, the use of the enteral route provides a safe and efficient means of delivering nutrition at a time of life when requirements are extremely high. In addition to high nutrient requirements in the early years of life, there are a number of specific pediatric conditions, such as failure to thrive, short bowel syndrome, and congenital heart disease, which place further demands on the growing child. These demands can be met through the careful use of enteral feeds. This article reviews the physiology and practical application of enteral feeding to the pediatric age group.

We used DNA fingerprinting by pulsed-field gel electrophoresis (PFGE), randomly amplified polymorphic DNA (RAPD) and PCR amplification of enterobacterial repetitive intergenic consensus sequences (ERIC-PCR) to compare 15 clinical isolates of Bordetella pertussis recovered between August 1993 and September 1995 from 13 infants and two adults, living in the same geographic area. PFGE produced 10 patterns and made it possible to differentiate all the isolates and to indicate an intrafamilial transmission. RAPD and ERIC-PCR generated banding patterns with small differences and had a poor discriminatory power. During the last 2 years, at Armand-Troussau pediatric hospital, 10 distinct clones of clinical B. pertussis isolates, with a predominant clone including seven strains, could be determined by the PFGE method.

The problem of characterizing thin layer ceramic deposited by plasma spraying has led the authors to develop an original means to determine materials, elastic constants by using a free vibration method. This paper gives an overview of an experimental set-up used for the elastic properties measurement of a free circular plate at room temperature or at higher temperature (1000 °C). This method is based on analysis of the natural frequencies of vibration recorded by a microphone. Identification of experimental natural frequencies and modal parameters that characterize the mode shapes, calculated analytically by using Mindlin theory, enables the Young's modulus and Poisson ratio of the material tested to be determined. Analytical and experimental results are compared over a frequency range from 0 to 20 kHz.

Characterization of highly fluorinated fullerenes (perfluorofullerenes) has revealed a wide range of x values. High reaction temperatures are limited by volatilization of the compounds. A good compromise is obtained for a reaction at 300 °C for several hours leading to a white C 60 F 54 compound with a narrow range of x values (± 2). X-ray powder diffraction reveals a f.c.c. lattice. Sublimation of C 60 F x compounds is carried out under static vacuum and separate fractions are condensed successively. As sublimation temperature is increased, fractions move from the liquid state to solids. 19 F NMR spectroscopy reveals a single narrow peak for liquid fractions, with a chemical shift of −72ppm/ CF 3 COOH thus suggesting a highly symmetrical species. The presence of oxygen is also detected when the starting material is exposed to air. The first fraction of air exposed compounds gives rise to a NMR signal at −55ppm. A relatively large quantity of liquid phase is obtained by direct condensation during C 60 fluorination. The NMR spectra is similar to that of the first sublimation fraction, exhibiting a peak at −72ppm.

Graphite oxide is a very hygroscopic compound and can accommodate up to 12wt% of water in its structure. Specific treatments afforded derivatives that present definitely no affinity for water and in which the hydroxy/epoxy ratio may be modified according to the treatment. These graphite oxide derivatives were characterized by X-ray powder diffraction, and IR and NMR spectroscopies. Electrochemical measurements were performed with these compounds as cathode material in liquid electrolyte lithium batteries.

Antileucoprotease (ALP) is generally considered as a specific marker for glandular serous cells, and plays a major role in the defence of the respiratory tract against proteolytic damage. Nevertheless, several studies have identified ALP in bronchial and bronchiolar surface epithelial cells, and also an increased number of ALP-containing cells in bronchiolar tissue during the development of pulmonary diseases. In order to define more clearly whether the surface epithelium might be involved in the defence of the respiratory mucosa, we have investigated the expression of ALP by cells of the nasal surface epithelium. Indirect immunocytochemistry and in situ hybridization for ALP were performed on human nasal polyp sections. The height of the surface epithelium, its morphology, and the degree of local inflammation were assessed in parallel. Surface epithelium morphology was highly heterogeneous. ALP-containing cells were identified, but only in remodelled areas of the surface epithelium (foldings, basal cell and/or mucous cell hyperplasia), with no association to the degree of inflammation. These results demonstrate that the surface epithelial cells of the human adult nasal mucosa can express ALP in remodelled surface epithelium, and may be actively involved in the biochemical defence of the airways.

PURPOSE The lack of pathologic breast cancer response to neoadjuvant chemotherapy (NCT), a negative prognostic factor, has prompted the addition of chemotherapy to adjuvant radiotherapy. This study aims to investigate prospectively the toxicities of adjuvant concurrent chemoradiotherapy versus radiotherapy alone. PATIENTS AND METHODS Two groups of patients treated for breast cancer between 1997 and 2002 by NCT, surgery, and radiotherapy with or without concurrent chemotherapy, were matched on age, body mass index (BMI), treatment period, treated side, and surgery type. Late toxicity was prospectively evaluated according to the CTCAE v3.0. Acute toxicity was derived from the medical charts. RESULTS A total of 52 patients were matched. Median follow-up was 10 years. Acute toxicity was higher in the chemoradiotherapy group compared with the radiotherapy alone group: 37% patients versus 10% experienced a grade 2/3 epithelitis (P=0.002); 48% versus 8% experienced a grade ≥1 mucositis (P=0.00001). Late toxicity was not significantly different in both univariate (51% vs. 49%; P=0.79) and multivariate analyses adjusted on the BMI (P=0.08). In univariate analysis, only the BMI tended to be predictive of toxicity (P=0.07). CONCLUSIONS Concurrent chemoradiotherapy after NCT and surgery was associated with increased acute toxicity but not long-term toxicity. The efficacy of this therapeutic strategy should be evaluated to better define its indications.

Patients with permanent cardiac pacemakers occasionally require radiotherapy. Therapeutic irradiation may cause pacemakers to malfunction due to the effects of ionizing radiation or electromagnetic interference. We studied the breast cancer patients who needed breast and/or chest wall and lymph node irradiation to assess the feasibility and tolerance in this population of patients.From November 2008 to December 2009, more than 900 patients received radiotherapy for their breast cancer in our department using megavoltage linear accelerator (X 4-6 MV and electrons). Among them, seven patients were with permanent pacemaker. All patients have been treated to the breast and chest wall and/or lymph nodes. Total dose to breast and/or chest wall was 50 Gy/25 fractions and 46 Gy/23 fractions to lymph nodes. Patients who underwent conserving surgery followed by breast irradiation were boosted when indicated to tumour bed with 16 Gy/8 fractions. All patients were monitored everyday in presence of radiation oncologist to follow the function of their pacemaker. All pacemakers were controlled before and after radiotherapy by the patients' cardiologist.Seven patients were referred in our department for postoperative breast cancer radiotherapy. Among them, only one patient was declined for radiotherapy and underwent mastectomy without radiotherapy. In four cases the pacemaker was repositioned before the beginning of radiotherapy. Six patients, aged between 48 and 84 years underwent irradiation for their breast cancer. Four patients were treated with conserving surgery followed by breast radiotherapy and two with mastectomy followed by chest wall and internal mammary chain, supra- and infra-clavicular lymph node irradiation. The dose to the pacemaker generator was kept below 2 Gy. There was no pacemaker dysfunction observed during the radiotherapy.The multidisciplinary work with position change of the pacemaker before radiotherapy and everyday monitoring permitted the safe treatment of our patients. Updated guidelines are definitely needed with more details about acceptable doses at the different parts of the pacemaker.

The radiation dose received by the eye depends on the pathology, tumour location (ocular globe, orbit, neighboring structures) and the radiation technique. The major complication is the complete loss of vision, which is often multifactorial. This article, based on a literature review, describes the radiation effects and the tolerance doses for all eye structures: cornea, lens, retina, optic nerves, orbit and ocular adnexa.