Dose and volume de-escalation of radiotherapy in head and neck cancer.

Radiotherapy plays a key role in the treatment of head and neck cancer. However, irradiation of the head and neck region is associated with high rates of acute and chronic toxicity. Technological advances have led to better visualisation of target volumes and critical structures and improved dose conformality in the treatment volume. Despite this, acute toxicity has not been substantially reduced and late toxicity has a significant impact on patients' quality of life. The greater radiosensitivity of tumours associated with the HPV and the development of new imaging techniques have encouraged research into new deintensified strategies to reduce the side effects of radiotherapy. The aim of this paper is to review the literature on the strategies of de-escalated treatment in dose and/or volume in head and neck cancer.

Comparison of whole-cell versus acellular pertussis vaccine effectiveness in school clusters of pertussis, France, 2013.

OBJECTIVES AND METHOD: We conducted a prospective study in 2013 to compare the whole-cell versus acellular pertussis vaccines effectiveness and duration of protection, following the occurrence of pertussis clusters. RESULTS: During seven school outbreaks, we identified 102 clinical pertussis cases, including 10 cases biologically confirmed by Bordetella pertussis specific PCR, among a cohort of 305 children in 2nd to 6th grade. The risk of pertussis when vaccinated with an acellular vaccine alone was 1.6 (RR=1.6; 95% CI=1.1-2.5) times higher than when vaccinated with a whole-cell vaccine or using a combined schedule. CONCLUSIONS: The limited duration of protection conferred by the acellular vaccine reinforces the 2013 introduction of the pertussis booster at six years old.

[Targeted screening of COPD in primary care: Feasibility and effectiveness]. / Détection précoce de la BPCO en soins primaires : un essai contrôlé randomisé.

INTRODUCTION: Chronic obstructive pulmonary disease (COPD) is a common but under-diagnosed pathology in primary care. The objective was to study the feasibility of a randomized controlled trial in general practice to detect new cases of COPD at an earlier stage. METHODS: A cluster randomized, controlled, multicenter intervention study comparing, according to a 2×2 factorial plan, two case finding strategies: a systematic GOLD-HAS hetero-questionnaire and coordination of the patient's path to facilitate access to spirometry. The PIL-DISCO pilot study took place in 2017. Patients between 40 and 80 years old, with no previous history of COPD, consulting their GP on a given day regardless of the reason, were included. RESULTS: 176 patients were included in 1.5 days. Spirometry was performed in none of the control arm, in 13 (29.5%) of the questionnaire arm, in 22 (50%) in the coordination arm and in 32 (72.7%) with the combination of the two strategies. Two cases of stage 2 COPD and thirteen other respiratory diseases were diagnosed. CONCLUSIONS: This study confirms the feasibility of the protocol in primary care in terms of speed of inclusion and acceptability. An extension phase aiming to include 3200 patients will assess the diagnostic value of the two strategies tested in general practice.

[Respiratory outcome of bronchopulmonary dysplasia in school-age children]. / Devenir respiratoire à l'âge scolaire de la dysplasie bronchopulmonaire.

BACKGROUND: Bronchopulmonary dysplasia (BPD) is the most common chronic lung disease of infancy. The influence of its initial severity on long-term respiratory outcome remains uncertain. OBJECTIVES: The purpose of this study was to examine the impact of "new BPD" on respiratory morbidity as well as respiratory function at rest and during exercise in school-age children. METHODS: The 93 preterm newborns (<33 weeks gestation) presenting with BPD between 1997 and 2004 at the Rennes University Hospital had been proposed for a specific follow-up program. The children included in this cohort and presenting without severe handicap or motor deficit were eligible for this observational retrospective study. Their standardized clinical evaluation and the results of the pulmonary function tests and cardiopulmonary exercise tests performed between the ages of 7 and 14 years were studied. BPD was considered to be moderate when respiratory or oxygen support continued at 36 weeks gestation with an FiO2 less than 30% and severe when FiO2 was greater than 30%. RESULTS: Among the 36 children assessed, the initial severity of the BPD was mild in 12 cases, moderate in 12 cases, and severe in 12 cases. The mean age at the time of the pulmonary function test (PFT) was 9.9 (±1.9) years, 19 children (53%) had respiratory symptoms during the year before the test, and six (17%) underwent long-term treatment. The PFT was abnormal for 32 children (89%): 23 showed airway obstruction, 16 hyperinflation, three increases in bronchial reactivity, and two restrictions. The residual volume/total lung capacity ratio was the only parameter related to the severity of BPD (P<0.05). The cardiopulmonary exercise test was given to 35 children: 15 of them had normal exercise ability but with a limited ventilatory reserve. CONCLUSIONS: Half of the children included in this "new-BPD" follow-up cohort had clinical respiratory morbidity and most of the children followed presented with persistent alterations in pulmonary function tests at school age, which were not associated with significant alterations in the maximum aerobic performance.

[AIRBAg study: preliminary results after one year of screening for COPD in dairy farmers]. / Étude AIRBAg : résultats préliminaires après un an de dépistage de la BPCO agricole.

INTRODUCTION: The AIRBAg study screens for bronchial obstruction in dairy farmers. We present the preliminary results after one year. METHODS: A prospective screening study based on questionnaires and electronic mini-spirometry (Néo-6(®)) that includes a representative sample of dairy farmers from the departments of Morbihan and Île-et-Vilaine in Brittany. The dairy farmers had an occupational medicine appointment and, if they demonstrated at least one marker of possible bronchial obstruction (chronic cough, chronic bronchitis, dyspnoea, wheezing, FEV1/FEV6<0.8), they were referred to a pulmonologist. The data we present here were extracted from the occupational medicine appointments because the pulmonologists' appointments are still running. RESULTS: Among the 277 dairy farmers included, 125 (45%) demonstrated "possible bronchial obstruction". The total score of the CAT questionnaire was higher in these farmers (9.1±6.2 versus 5.8±4.0; P<0.0001). In multivariate analysis markers of "possible bronchial obstruction" were eczema, manual foddering and duration of mechanical straw litter spreading. CONCLUSION: Occupational medicine appointments identified markers of "possible bronchial obstruction". We will have the complete results from AIRBAg study in 2015.

Which pelvic ring fractures are potentially lethal?

PURPOSE: Global mortality of polytraumatised patients presenting pelvic ring fractures remains high (330%), despite improvements in treatment algorithms in Level I Trauma Centers. Many classifications have been developed in order to identify and analyse these pelvic ring lesions. However, it remains difficult to predict intra-pelvic haemorrhage. The aim of this study was to identify pelvic ring anatomical lesions associated with significant blood loss, susceptible to lead to life-threatening haemorrhage. MATERIAL AND METHOD: This study focused on a retrospective analysis of patients' medical files, all of whom were admitted to one of the shock rooms of Grenoble University Hospital, France, between January 2004 and December 2008. Treatment was given according to the institutional algorithm of the Alps Trauma Center and Emergency North Alpine Network Trauma System (TRENAU). Different hemodynamical parameters at arrival were measured, and the fractures were classified according to Young and Burgess, Tile, Letournel and Denis. One hundred and ninety seven patients were analysed. They were subdivided into two groups, embolised (Group E) and non-embolised (Group NE). RESULTS: Group NE included 171 patients with a mean age of 40.2 ± 8.7 years (15-90). Group E included 26 patients with a mean age of 41.6 ± 5.3 years (18-67). Twenty-six patients died during the initial treatment phase. Eleven belonged to Group E and 15 to Group NE. Mortality was significantly higher in Group E (42.3% vs 8.8% in Group NE) (p < 0.05). There were significantly many more Tile C unstable fractures in Group E (p = 0.0014), and anterior lesions, according to Letournel, with pubic symphysis disruption were significantly more likely to lead to active bleeding treated by selective embolisation (p = 0.0014). Posterior pelvic ring lesions with iliac wing fracture and transforaminal sacral fractures (Denis 2) were also more frequently associated with bleeding treated by embolisation (p = 0.0088 and p = 0.0369 respectively). DISCUSSION/CONCLUSION: It appears that in our series the primary identification and classification of osteo-ligamentous lesions (according to Letournel and Denis' classifications) allows to anticipate the importance of bleeding and to adapt the management of patients accordingly, in order to quickly organise angiography with embolisation.

Influence of vitamin E acetate and other lipids on the phase behavior of mesophases based on unsaturated monoglycerides.

The phase behavior of the ternary unsaturated monoglycerides (UMG)-DL-α-tocopheryl acetate-water system has been studied. The effects of lipid composition in both bulk and dispersed lyotropic liquid crystalline phases and microemulsions were investigated. In excess water, progressive addition of DL-α-tocopheryl acetate to a binary UMG mixture results in the following phase sequence: reversed bicontinuous cubic phase, reversed hexagonal (H(II)) phase, and a reversed microemulsion. The action of DL-α-tocopheryl acetate is then compared to that of other lipids such as triolein, limonene, tetradecane, and DL-α-tocopherol. The impact of solubilizing these hydrophobic molecules on the UMG-water phase behavior shows some common features. However, the solubilization of certain molecules, like DL-α-tocopherol, leads to the presence of the reversed micellar cubic phase (space group number 227 and symmetry Fd3m) while the solubilization of others does not. These differences in phase behavior are discussed in terms of physical-chemical characteristics of the added lipid molecule and its interaction with UMG and water. From an applications point of view, phase behavior as a function of the solubilized content of guest molecules (lipid additive in our case) is crucial since macroscopic properties such as molecular release depend strongly on the phase present. The effect of two hydrophilic emulsifiers, used to stabilize the aqueous dispersions of UMG, was studied and compared. Those were Pluronic F127, which is the most commonly used stabilizer for these kinds of inverted type structures, and the partially hydrolyzed emulsifier lecithin (Emultop EP), which is a well accepted food-grade emulsifier. The phase behavior of particles stabilized by the partially hydrolyzed lecithin is similar to that of bulk sample at full hydration, but this emulsifier interacts significantly with the internal structure and affects it much more than F127.

Microbiological changes and diversity in autochthonous non-toxigenic Corynebacterium diphtheriae isolated in France.

Autochtonous toxigenic Corynebacterium diphtheriae have disappeared in mainland France, but non-toxigenic C. diphtheriae are still circulating. Using phenotypic and molecular tools, we retrospectively characterized 103 non-toxigenic C. diphtheriae collected in mainland France and highlight several changes. The proportion of C. diphtheriae belfanti increased between 1977 and 2011 and it is the most frequent biotype recovered in recent years. Resistance to ciprofloxacin has increased and most isolates with decreased sensitivity belong to the belfanti biotype. Using multilocus sequence typing, we demonstrate that French isolates are distributed in a large number of sequence types and identify three distinct lineages. C. diphtheriae mitis and gravis form lineage I while C. diphtheriae belfanti forms lineages II and III. Almost all isolates of lineage II are part of a unique clonal complex or are very close to it. Most French isolates have a dtxR sequence homologous to that of toxigenic isolates, suggesting that if lyzogenised by a corynephage, they can express diphtheria toxin.

Long-term evaluation of respiratory status after esophageal atresia repair.

RATIONALE: Esophageal atresia (EA) is a congenital malformation. Nowadays, its initial prognosis is excellent thanks to improvements in neonatal and surgical management. However, the assessment of long-term respiratory outcome has become necessary in affected children and was thus performed in this study. The benefits of cardiopulmonary function testing were also examined. METHODS: The medical records of 77 children operated on for EA between 1990 and 2004 were reviewed. The results of respiratory function testing and cardiopulmonary response to effort were collected, together with neonatal and anthropometric data. RESULTS: Acceptable measurements were obtained in 31 children with EA. These children were comparable to the ones lost during follow-up. The results of pulmonary function tests (PFTs) were abnormal in 21 cases (68%). A poor ventilatory response was detected in 14 children (45%) by cardiopulmonary function testing. Ten children who had abnormal results on PFTs were not under any anti-asthmatic treatment. CONCLUSIONS: Impaired lung function was noted in children with repaired EA. Indeed, cardiopulmonary function tests results correlated with standard spirometric parameters and revealed minimal clinical symptoms. Moreover, many children with EA had a limited ventilatory reserve (VR). These results indicate that respiratory symptoms are often neglected in children with repaired EA and reinforce the need to provide adequate treatment.

Insertion sequences shared by Bordetella species and implications for the biological diagnosis of pertussis syndrome.

The molecular diagnosis of pertussis and parapertussis syndromes is based on the detection of insertion sequences (IS) 481 and 1001, respectively. However, these IS are also detected in the genomes of various Bordetella species, such that they are not specific for either B. pertussis or B. parapertussis. Therefore, we screened the genome of recently circulating isolates of Bordetella species to compare the prevalence of IS481, IS1001 and, also IS1002 with previously published data and to sequence all IS detected. We also investigated whether the numbers of IS481 and IS1001 copies vary in recently circulating isolates of the different Bordetella species. We used the polymerase chain reaction (PCR) method for screening the genome of circulating isolates and to prepare the fragments for sequencing. We used Southern blotting and quantitative real-time PCR for quantification of the numbers of IS. We found no significant diversity in the sequences of the IS harboured in the genomes of the Bordetella isolates screened, except for a 71-nucleotide deletion from IS1002 in B. bronchiseptica. The IS copy numbers in the genome of recently circulating isolates were similar to those in reference strains. Our results confirm that biological diagnosis targeting the IS481 and IS1001 elements are not specific and detect the species B. pertussis, B. holmesii and B. bronchiseptica (IS481), and B. parapertussis and B. bronchiseptica (IS1001).

Clarithromycin stops lung function decline in airway-centered interstitial fibrosis.

Airway-centered interstitial fibrosis (ACIF) is a distinct type of lung interstitial fibrosis characterized by lesions centered on the airways. Several cases reported in the literature showed little to no effect of corticosteroids and a high mortality rate in the absence of lung transplantation. No other efficient approach is described for the treatment of this type of fibrosis. We report for the first time the case of a 44-year-old patient diagnosed with ACIF on surgical lung biopsy and stabilized with clarithromycin after failure of systemic corticosteroids. We need to confirm this benefit in other patients to ascertain the anti-inflammatory effect of macrolides, which are far less harmful compared to corticosteroids or immunosuppressant drugs.

Evolution of French Bordetella pertussis and Bordetella parapertussis isolates: increase of Bordetellae not expressing pertactin.

Bordetella pertussis and Bordetella parapertussis are closely related bacterial agents of whooping cough. Whole-cell pertussis (wP) vaccine was introduced in France in 1959. Acellular pertussis (aP) vaccine was introduced in 1998 as an adolescent booster and was rapidly generalized to the whole population, changing herd immunity by specifically targeting the virulence of the bacteria. We performed a temporal analysis of all French B. pertussis and B. parapertussis isolates collected since 2000 under aP vaccine pressure, using pulsed-field gel electrophoresis (PFGE), genotyping and detection of expression of virulence factors. Particular isolates were selected according to their different phenotype and PFGE type and their characteristics were analysed using the murine model of respiratory infection and in vitro cell cytotoxic assay. Since the introduction of the aP vaccines there has been a steady increase in the number of B. pertussis and B. parapertussis isolates collected that are lacking expression of pertactin. These isolates seem to be as virulent as those expressing all virulence factors according to animal and cellular models of infection. Whereas wP vaccine-induced immunity led to a monomorphic population of B. pertussis, aP vaccine-induced immunity enabled the number of circulating B. pertussis and B. parapertussis isolates not expressing virulence factors to increase, sustaining our previous hypothesis.

Characterization and comparison of invasive Corynebacterium diphtheriae isolates from France and Poland.

Corynebacterium diphtheriae, the agent of diphtheria, is rarely responsible for bacteremia. However, high numbers of bacteremia have been reported in countries with extensive immunization coverage. Here, we used molecular and phenotypic tools to characterize and compare 42 invasive isolates collected in France (including New Caledonia) and Poland over a 23-year period.

Internal organisation in polyelectrolytes/oppositely charged surfactants colloidal complexes anticipating precipitated nanostructures.

In this paper, we relate the periodic nanostructures found in the colloidal complexes and the concentrated phases obtained with polyelectrolyte/surfactant aqueous solutions. We present small-angle X-ray scattering studies of the self-organisation of the anionic polymer carboxymethylcellulose with three cationic quaternary ammonium surfactants with different head and tail groups: hexadecyl trimethyl, hexadecyl ethyl dimethyl and didodecyl dimethyl ammonium bromides. We investigated the mesophases obtained above a precipitation threshold. The mixed solutions with the double-chained surfactant led to lamellar phases, in which the repeat distance only depends on the surfactant/carboxyl charge molar ratio. We show that an internal lamellar organisation already takes place in the dilute phase containing colloidal complexes found below the precipitation threshold.

Comparison of arsenic concentrations in simultaneously-collected groundwater and aquifer particles from Bangladesh, India, Vietnam, and Nepal.

One of the reasons the processes resulting in As release to groundwater in southern Asia remain poorly understood is the high degree of spatial variability of physical and chemical properties in shallow aquifers. In an attempt to overcome this difficulty, a simple device that collects groundwater and sediment as a slurry from precisely the same interval was developed in Bangladesh. Recently published results from Bangladesh and India relying on the needle-sampler are augmented here with new data from 37 intervals of grey aquifer material of likely Holocene age in Vietnam and Nepal. A total of 145 samples of filtered groundwater ranging in depth from 3 to 36 m that were analyzed for As (1-1000 mug/L), Fe (0.01-40 mg/L), Mn (0.2-4 mg/L) and S (0.04-14 mg/L) are compared. The P-extractable (0.01-36 mg/kg) and HCl-extractable As (0.04-36 mg/kg) content of the particulate phase was determined in the same suite of samples, in addition to Fe(II)/Fe ratios (0.2-1.0) in the acid-leachable fraction of the particulate phase. Needle-sampler data from Bangladesh indicated a relationship between dissolved As in groundwater and P-extractable As in the particulate phase that was interpreted as an indication of adsorptive equilibrium, under sufficiently reducing conditions, across 3 orders of magnitude in concentrations according to a distribution coefficient of 4 mL/g. The more recent observations from India, Vietnam and Nepal show groundwater As concentrations that are often an order of magnitude lower at a given level of P-extractable As compared to Bangladesh, even if only the subset of particularly reducing intervals characterized by leachable Fe(II)/Fe >0.5 and dissolved Fe >0.2 mg/L are considered. Without attempting to explain why As appears to be particularly mobile in reducing aquifers of Bangladesh compared to the other regions, the consequences of increasing the distribution coefficient for As between the particulate and dissolved phase to 40 mL/g for the flushing of shallow aquifers of their initial As content are explored.

Nanostructures of colloidal complexes formed in oppositely charged polyelectrolyte/surfactant dilute aqueous solutions.

Small-angle neutron scattering measurements were performed on dilute solutions of carboxymethylcellulose/DTAB complexes in water in order to determine their size, shape and internal structures. At low polymer content, the complexes are spherical, rather monodisperse and probably made of polymer chains intercalated between surfactant micelles. Moreover, we show that these micelles have a similar cubic arrangement than found in polymer/surfactant precipitates formed at higher surfactant concentrations. At larger polymer content, in the semi-dilute polyelectrolyte regime, the complexes are larger, softer and polydisperse. However, they possess a similar internal structure in both regimes. Carboxymethylcellulose/CTAB complexes are also large, soft and polydisperse but do not seem to exhibit well-defined internal structures.

Circulation of a type 1 recombinant vaccine-derived poliovirus strain in a limited area in Romania.

After intensive immunisation campaigns with the oral polio vaccine (OPV) as part of the Global Polio Eradication Initiative, poliomyelitis due to wild viruses has disappeared from most parts of the world, including Europe. Here, we report the characterization of a serotype 1 vaccine-derived poliovirus (VDPV) isolated from one acute flaccid paralysis (AFP) case with tetraplegia and eight healthy contacts belonging to the same small socio-cultural group having a low vaccine coverage living in a small town in Romania. The genomes of the isolated strains appeared to be tripartite type 1/type 2/type 1 vaccine intertypic recombinant genomes derived from a common ancestor strain. The presence of 1.2% nucleotide substitutions in the VP1 capsid protein coding region of most of the strains indicated a circulation time of about 14 months. These VDPVs were thermoresistant and, in transgenic mice expressing the human poliovirus receptor, appeared to have lost the attenuated phenotype. These results suggest that small populations with low vaccine coverage living in globally well-vaccinated countries can be the origin of VDPV emergence and circulation. These results reaffirm the importance of active surveillance for acute flaccid paralysis and poliovirus in both polio-free and polio-endemic countries.

[Interpreting carbon monoxide transfer coefficient: significance and difficulties]. / Intérêts et difficultés d'interprétation du coefficient de transfert du CO (TLCO/VA).

INTRODUCTION: Interpreting measurements of carbon monoxide can be problematic. STATE OF THE ART: The transfer factor (TLCO) is usually calculated by multiplying the decrease in alveolar CO concentration between the beginning and the end of a 10 second breath hold (KCO) by the alveolar volume (VA). Thus a reduced TLCO may occur due to either a low KCO, a reduced VA, or a combination of both. PERSPECTIVES: A careful examination of KCO and VA will usually suggest a specific explanation for a reduction in TLCO. In restrictive lung diseases from extrapulmonary origin, TLCO is low but TLCO/VA [[/INF 120% of the reference values. In interstitial lung disease, the value of TLCO/VA depends on whether the loss of lung units is diffuse or not, and probably also on the status of the microcirculation. In airflow obstruction, a low VA is caused by uneven distribution of inspired He/CO mixture within the breath-hold time. CONCLUSIONS: The transfer factor for carbon monoxide is best interpreted in terms of its components, alveolar volume and carbon monoxide transfer coefficient.

Advances and prospects on biosynthesis, structures and functions of venom proteins from parasitic wasps.

Molecular and biochemical properties of parasitoid Hymenoptera's venom proteins are currently receiving an increasing interest. In this review, we will highlight the progress that has been made over the past 10 years in fundamental research on this field. Main knowledge acquired on the structural features of parasitoid venom peptides, proteins and enzymes will be summarized and discussed and several examples showing the diversity of their biological functions will be given with respect to future prospects and applications.

Asobara, braconid parasitoids of Drosophila larvae: unusual strategies to avoid encapsulation without VLPs.

Ichneumonoidae parasitoids have been well described for their regulatory effects on host physiology which are usually associated with the activity of polydnaviruses (PDVs) or viruslike-particles (VLPs) injected by the female wasps at oviposition. Among them, parasitoids of the braconid families display specific characteristics like the required activity of secretions from the maternal venom glands or of teratocytes from embryological origin. However, none of these features were observed in two braconid species of the Asobara genus parasitizing Drosophila hosts. In the absence of PDVs and VLPs, the two species A. tabida and A. citri seem to have developed unique strategies to avoid immunity defenses and to succeed in their Drosophila larval hosts. The aim of this study is to report on the complex relationships of braconid parasitoids with their hosts and to present some of the insights from studying Drosophila parasitoids.