Importance of whole genome sequencing for the assessment of outbreaks in diagnostic laboratories: analysis of a case series of invasive Streptococcus pyogenes infections.

Outbreaks of Streptococcus pyogenes hypervirulent clones are constant public health threats. In western Switzerland, an increase of severe cases of S. pyogenes invasive infections was observed between December 2015 and March 2016. Our aim was (i) to investigate these cases by the use of Whole Genome Sequencing (WGS) and (ii) to determine the specific virulome and resistome of each isolate in order to undertake adequate public health measures. Eleven Streptococcus pyogenes strains isolated from 11 patients with severe invasive infections between December 13, 2015 and March 12, 2016 were included in our study. Practically, emm-typing, MLST and WGS were used to investigate the relatedness between the isolates. The presence of virulence and antibiotic resistance genes as well as mutations in transcriptional regulators of virulence and in genes encoding for antibiotic targets were assessed. Three and two groups of isolates shared the same emm-type and ST type, respectively. Single Nucleotide Polymorphism (SNP) analysis revealed 14 to 32 SNPs between the strains of the same emm-type group, ruling out the possibility of a clonal outbreak. Mutations found in covS and rocA could partially explain an increased virulence. As these reassuring results were obtained in less than 10 days, no specific hospital hygiene and no dedicated public health measures had to be undertaken. WGS is a powerful technique to discriminate between closely related strains, excluding an outbreak in less than 10 days. Moreover, WGS provided extensive data on the virulome and resistome of all these strains.

Impact of neoadjuvant chemotherapy cycles prior to interval surgery in patients with advanced epithelial ovarian cancer.

OBJECTIVES: Complete surgery with no macroscopic residual disease (RD) at primary (PDS) or interval debulking surgery (IDS) is the main objective of surgery in advanced epithelial ovarian cancer (EOC). The aim of this work was to evaluate the impact on survival of the number of neoadjuvant chemotherapy (NAC) cycles before IDS in EOC patients. METHODS: Data from EOC patients (stages IIIC-IV), operated on between 1995 and 2010 were consecutively recorded. NAC/IDS patients were analyzed according to the number of preoperative cycles (<4=group B1; >4=group B2) and compared with patients receiving PDS (group A). Patients with complete resection were specifically analyzed. RESULTS: 367 patients were analyzed, 220 received PDS and 147 had IDS/NAC. In group B, 37 patients received more than 4 NAC cycles (group B2). Group B2 patients presented more frequently stage IV disease at diagnosis (p<0.01) compared to groups A and B1. The rate of complete cytoreduction was higher in group B (p<0.001). Patients with no RD after IDS and who had received more than 4 NAC cycles had poor survival (p<0.001) despite complete removal of their tumor (relative risk of death after multivariate analysis of 3 (p<0.001)) with an independent impact from disease stage and WHO performance status. CONCLUSIONS: Patients with advanced EOC receiving complete IDS after more than 4cycles of NAC have poor prognosis. Despite worse prognostic factors observed in this group of patients, our study reinforces the concept of early and complete removal of all macroscopic tumors in the therapeutic sequence of EOC.

Local reference levels and organ doses from pediatric cardiac interventional procedures.

Interventional cardiology (IC) procedures can be responsible for relatively high radiation doses compared to conventional radiology especially for young patients. The aim of this study was to assess current exposure levels in a French reference centre of pediatric IC. Dosimetric data including dose area product (DAP), fluoroscopy time (FT) and number of cine frame (NF) were analysed taking into account patient weight. Doses to the lungs, esophagus, breast and thyroid were evaluated using anthropomorphic phantoms and thermoluminescent dosimeters. Finally, effective doses (E) were calculated using DAP and conversion factors calculated with PCXMC 2.0 software. 801 IC procedures performed between 2010 and 2011 were analysed. Large variations were observed for DAP, FT and NF values for a given procedure and a given weight group. The assessment of organ doses showed high levels of dose to the lungs and esophagus especially in new-born babies. For diagnostic procedures, E varied from 0.3 to 23 mSv with a mean value of 4.8 mSv and for therapeutic procedures, values ranged from 0.1 to 48.4 mSv with a mean value of 7.3 mSv. The highest values were recorded for angioplasty procedures (mean 13 mSv, range 0.6-48.4 mSv). The increasing use of IC in pediatric population stresses the need of setting up reference levels and keeping doses to children as low as possible.

[Impact of surgery in the management of pancreatic metastases of renal cell cancer]. / Place de la chirurgie dans la prise en charge des métastases pancréatiques des cancers du rein.

INTRODUCTION: Incidence of renal cell carcinoma (RCC) is increasing over the 25 last years. Pancreatic metastases of RCC are rare. The aim of this work was to study overall survival of patients operated for pancreatic metastases of RCC in Montpellier cancer institute. PATIENTS AND METHODS: Between 2000 and 2012, a retrospective monocentric study was performed at Montpellier cancer institute. We evaluated the outcomes of curative pancreatic metastases from renal primary and the impact of targeted therapies. RESULTS: Thirty-eight patients were treated in our center for pancreatic metastases of RCC. Twelve patients had a curative surgery of metachronous pancreatic metastases. Four patients were without recurrence after pancreatic resection (33.3%). None had adjuvant therapy. Six patients were treated by targeted therapies, because of metastatic progression. Five of 6 died, the sixth evolved with targeted therapies by thyrosine kinase inhibitor. Average deadline between appearance of metastases and death was 89.9 months for operated patients. Average deadline between appearance of c metastases and death was 33.1 months for the others (P=0.004). CONCLUSION: Surgical treatment of pancreatic metastases should increase life expectancy of patients. Others studies are necessary to prove the impact of targeted therapies in metastatics patients in this indication. LEVEL OF EVIDENCE: 5.

X-Ray to DRR Images Translation for Efficient Multiple Objects Similarity Measures in Deformable Model 3D/2D Registration.

The robustness and accuracy of the intensity-based 3D/2D registration of a 3D model on planar X-ray image(s) is related to the quality of the image correspondences between the digitally reconstructed radiographs (DRR) generated from the 3D models (varying image) and the X-ray images (fixed target). While much effort may be devoted to generating realistic DRR that are similar to real X-rays (using complex X-ray simulation, adding densities information in 3D models, etc.), significant differences still remain between DRR and real X-ray images. Differences such as the presence of adjacent or superimposed soft tissue and bony or foreign structures lead to image matching difficulties and decrease the 3D/2D registration performance. In the proposed method, the X-ray images were converted into DRR images using a GAN-based cross-modality image-to-images translation. With this added prior step of XRAY-to-DRR translation, standard similarity measures become efficient even when using simple and fast DRR projection. For both images to match, they must belong to the same image domain and essentially contain the same kind of information. The XRAY-to-DRR translation also addresses the well-known issue of registering an object in a scene composed of multiple objects by separating the superimposed or/and adjacent objects to avoid mismatching across similar structures. We applied the proposed method to the 3D/2D fine registration of vertebra deformable models to biplanar radiographs of the spine. We showed that the XRAY-to-DRR translation enhances the registration results, by increasing the capture range and decreasing dependence on the similarity measure choice since the multi-modal registration becomes mono-modal.

Semi-automated stereoradiographic upper limb 3D reconstructions using a combined parametric and statistical model: a preliminary study.

PURPOSE: Quantitative assessment of 3D clinical indices may be crucial for elbow surgery planning. 3D parametric modeling from bi-planar radiographs was successfully proposed for spine and lower limb clinical investigation as an alternative for CT-scan. The aim of this study was to adapt this method to the upper limb with a preliminary validation. METHODS: CT-scan 3D models of humerus, radius and ulna were obtained from 20 cadaveric upper limbs and yielded parametric models made of geometric primitives. Primitives were defined by descriptor parameters (diameters, angles...) and correlations between these descriptors were found. Using these correlations, a semi-automated reconstruction method of humerus using bi-planar radiographs was achieved: a 3D personalized parametric model was built, from which clinical parameters were computed [orientation and projections on bone surface of trochlea sulcus to capitulum (CTS) axis, trochlea sulcus anterior offset and width of distal humeral epiphysis]. This method was evaluated by accuracy compared to CT-scan and reproducibility. RESULTS: Points-to-surface mean distance was 0.9 mm (2 RMS = 2.5 mm). For clinical parameters, mean differences were 0.4-1.9 mm and from 1.7° to 2.3°. All parameters except from angle formed by CTS axis and bi-epicondylar axis in transverse plane were reproducible. Reconstruction time was about 5 min. CONCLUSIONS: The presented method provides access to morphological upper limb parameters with very low level of radiation. Preliminary in vitro validation for humerus showed that it is fast and accurate enough to be used in clinical daily practice as an alternative to CT-scan for total elbow arthroplasty pre operative evaluation.

Measurement of |V(cb)| and the form-factor slope in B --> Dl- nu(l) decays in events tagged by a fully reconstructed B meson.

We present a measurement of the Cabibbo-Kobayashi-Maskawa matrix element |V(cb)| and the form-factor slope rho2 in B --> Dl- nu(l) decays based on 460x10(6) BB events recorded at the Upsilon(4S) resonance with the BABAR detector. B --> Dl- nu(l) decays are selected in events in which a hadronic decay of the second B meson is fully reconstructed. We measure B(B- --> D0 l- nu(l))/B(B- --> Xl- nu(l)) = (0.255+/-0.009+/-0.009) and B(B0 --> D+ l- nu(l))/B(B0 --> Xl- nu(l)) = (0.230+/-0.011+/-0.011), along with the differential decay distribution in B --> Dl- nu(l) decays. We then determine G(1)|V(cb)| = (42.3+/-1.9+/-1.4)x10(-3) and rho2 = 1.20+/-0.09+/-0.04, where G(1) is the hadronic form factor at the point of zero recoil.

Searches for Lepton flavor violation in the decays tau{+/-}-->e{+/-}gamma and tau{+/-}-->mu{+/-}gamma.

Searches for lepton-flavor-violating decays of a tau lepton to a lighter mass lepton and a photon have been performed with the entire data set of (963+/-7)x10{6} tau decays collected by the BABAR detector near the Upsilon(4S), Upsilon(3S) and Upsilon(2S) resonances. The searches yield no evidence of signals and we set upper limits on the branching fractions of B(tau{+/-}-->e{+/-}gamma)<3.3x10{-8} and B(tau{+/-}-->mu{+/-}gamma)<4.4x10{-8} at 90% confidence level.

Measurements of charged current lepton universality and |Vus| using tau lepton decays to e- ν(e) ν(τ), µ- ν(µ) ν(τ), π- ν(τ), and K- ν(τ).

Using 467 fb(-1) of e+e- annihilation data collected with the BABAR detector, we measure (B(τ- → µ- ν(µ) ν(τ)))/(B(τ- → e- ν(e) ν(τ))) =(0.9796±0.0016±0.0036), (B(τ- → π- ν(τ)))/(B(τ- → e- ν(e) ν(τ))) = (0.5945±0.0014±0.0061), and (B(τ- → K- ν(τ)))/(B(τ- → e- ν(e) ν(τ))) = (0.03882±0.00032±0.00057), where the uncertainties are statistical and systematic, respectively. From these precision τ measurements, we test the standard model assumption of µ-e and τ-µ charge current lepton universality and provide determinations of |Vus| experimentally independent of the decay of a kaon.

[The framework of radiation protection in France]. / Organisation de la radioprotection en France.

Over the last 10 years, the framework of radiation protection in France has undergone significant modifications. This has mainly been the result of implementation of European directives, which are based on new data and evolving concepts at the international level. As a practical matter, public health laws and labor laws have evolved to strengthen the radiation protection to both patients and workers. For patients, the indication for the examination must be better justified and the exposure should be optimized and recorded. For workers, the maximum exposure limits have been reduced while monitoring and risk assessment have been reinforced. In addition, the equipment is subject to additional quality control evaluations while the facilities are assessed for safety.

[Typical patient radiation doses in diagnostic imaging]. / Ordre de grandeur des doses délivrées en radiodiagnostic.

Radiologists should be able to appreciate the radiation dose delivered to patients for routine diagnostic procedures. The radiology report should include data necessary to calculate the patient dose in Gray. Using the effective dose, it is possible to compare with other source of radiation exposure. Simple formulas, taking into account different anatomical regions, derived from dose-area product (conventional radiography) or dose-length product (CT) are provided to calculate the effective dose in Sievert. For conventional (non-interventional) radiography, the effective dose for a given exam is inferior or equal to the yearly background radiation. For CT, the effective dose corresponds to 1 to 10 years of yearly background radiation.

Measurement of D{0}-D[-over]{0} mixing from a time-dependent amplitude analysis of D{0}-->K+pi{-}pi{0} decays.

We present evidence of D{0}-D[-over ]{0} mixing using a time-dependent amplitude analysis of the decay D{0}-->K+pi{-}pi;{0} in a data sample of 384 fb{-1} collected with the BABAR detector at the PEP-II e+e{-} collider at the Stanford Linear Accelerator Center. Assuming CP conservation, we measure the mixing parameters x{Kpipi{0}}{'}=[2.61{-0.68}{+0.57}(stat)+/-0.39(syst)]%, y{Kpipi;{0}}{'}=[-0.06{-0.64}{+0.55}(stat)+/-0.34(syst)]%. This result is inconsistent with the no-mixing hypothesis with a significance of 3.2 standard deviations. We find no evidence of CP violation in mixing.

Measurement of B-->K{*}(892)gamma branching fractions and CP and Isospin asymmetries.

We present an analysis of the decays B{0}-->K{*0}(892)gamma and B{+}-->K{*+}(892)gamma using a sample of about 383 x 10{6} BB[-over ] events collected with the BABAR detector at the PEP-II asymmetric energy B factory. We measure the branching fractions B(B{0}-->K{*0}gamma)=(4.47+/-0.10+/-0.16) x 10{-5} and B(B{+}-->K{*+}gamma)=(4.22+/-0.14+/-0.16) x 10{-5}. We constrain the direct CP asymmetry to be -0.033K{*}gamma)<0.028 and the isospin asymmetry to be 0.017

Precise measurement of the e+e- --> pi+pi-(gamma) cross section with the initial state radiation method at BABAR.

A precise measurement of the cross section of the process e(+)e(-) --> pi(+)pi(-)(gamma) from threshold to an energy of 3 GeV is obtained with the initial state radiation (ISR) method using 232 fb(-1) of data collected with the BABAR detector at e(+)e(-) center-of-mass energies near 10.6 GeV. The ISR luminosity is determined from a study of the leptonic process e(+)e(-) --> mu(+)mu(-)gamma(gamma). The leading-order hadronic contribution to the muon magnetic anomaly calculated using the pipi cross section measured from threshold to 1.8 GeV is (514.1 +/- 2.2(stat) +/- 3.1(syst)) x 10(-10).

Search for invisible decays of the Upsilon(1S).

We search for invisible decays of the Upsilon(1S) meson using a sample of 91.4 x 10(6) Upsilon(3S) mesons collected at the BABAR/PEP-II B factory. We select events containing the decay Upsilon(3S) --> pi(+)pi(-)Upsilon(1S) and search for evidence of an undetectable Upsilon(1S) decay recoiling against the dipion system. We set an upper limit on the branching fraction B(Upsilon(1S) --> invisible) < 3.0 x 10(-4) at the 90% confidence level.

Evidence for the eta(b)(1S) meson in radiative Upsilon(2S) decay.

We have performed a search for the eta_{b}(1S) meson in the radiative decay of the Upsilon(2S) resonance using a sample of 91.6x10(6) Upsilon(2S) events recorded with the BABAR detector at the PEP-II B factory at the SLAC National Accelerator Laboratory. We observe a peak in the photon energy spectrum at Egamma=609.3(-4.5)(+4.6)(stat)+/-1.9(syst) MeV, corresponding to an eta(b)(1S) mass of 9394.2(-4.9)(+4.8)(stat)+/-2.0(syst) MeV/c2. The branching fraction for the decay Upsilon(2S)-->gamma(eta)b(1S) is determined to be [3.9+/-1.1(stat)-0.9+1.1(syst)]x10(-4). We find the ratio of branching fractions B[Upsilon(2S)-->gamma(eta)b(1S)]/B[Upsilon(3S)-->gamma(eta)b(1S)]=0.82+/-0.24(stat)(-0.19)(+0.20)(syst).

Search for a low-mass higgs boson in Upsilon(3S)-->gammaA(0), A(0)-->tau(+)tau(-) at BABAR.

We search for a light Higgs boson A0 in the radiative decay Upsilon(3S)-->gammaA(0), A(0)-->tau+tau-, tau+-->e+nu(e)nu(tau), or tau+-->mu+nu(mu)nu(tau). The data sample contains 122x10(6) Upsilon(3S) events recorded with the BABAR detector. We find no evidence for a narrow structure in the studied tau+tau- invariant mass region of 4.03gammaA(0))xB(A(0)-->tau+tau-)>(1.5-16)x10(-5) across the m(tau+tau-) range. We also set a 90% C.L. upper limit on the tau+tau- decay of the eta(b) at B(eta(b)-->tau+tau-)<8%.

Total laparoscopic radical hysterectomy for locally advanced cervical carcinoma (stages IIB, IIA and bulky stages IB) after concurrent chemoradiation therapy: surgical morbidity and oncological results.

OBJECTIVES: To evaluate the surgical outcome and the oncologic results of total laparoscopic radical hysterectomy (TLRH) after neoadjuvant chemoradiation therapy (CRT) for locally advanced cervical carcinoma. METHODS: All patients who underwent TLRH after CRT for stages IIB-IIA and bulky IB diseases were reviewed. The control group for this analysis was a cohort of patients treated with abdominal radical hysterectomy (ARH) after CRT for the same stage cancers. RESULTS: We reviewed 102 patients operated on between 2000 and 2008 (46 TLRH and 56 ARH). Mean age at diagnosis was 44 years, and mean B.M.I was 22.1. There was no difference in tumor characteristics between the two groups. Seven patients in the laparoscopic group required conversion to laparotomy (15%). Mean estimated blood loss (200 vs. 400 mL, p<0.01) and the median duration of hospital stay (5 vs. 8 days, p<0.01) were significantly lower in the laparoscopic group. Morbidity rates and urinary complications were reduced in the laparoscopic group (p=0.04). Local recurrence rates, disease-free and overall survival were comparable in the two groups. Best survival was observed for patients with pathological complete response or microscopic residual disease compared to patients with macroscopic residues (p<0.01). CONCLUSIONS: Radical hysterectomy after CRT is known to be difficult with significant morbidity rates and remains controversial in comparison to exclusive CRT. TLRH after preoperative CRT is feasible for patients with locally advanced cervical cancer in 85% of the cases. For these patients, TLRH compared with ARH was associated with favorable surgical outcome with comparable oncological results.

The relevance of image quality indices for dose optimization in abdominal multi-detector row CT in children: experimental assessment with pediatric phantoms.

This study assessed and compared various image quality indices in order to manage the dose of pediatric abdominal MDCT protocols and to provide guidance on dose reduction. PMMA phantoms representing average body diameters at birth, 1 year, 5 years, 10 years and 15 years of age were scanned in a four-channel MDCT with a standard pediatric abdominal CT protocol. Image noise (SD, standard deviation of CT number), noise derivative (ND, derivative of the function of noise with respect to dose) and contrast-to-noise ratio (CNR) were measured. The 'relative' low-contrast detectability (rLCD) was introduced as a new quantity to adjust LCD to the various phantom diameters on the basis of the LCD(1%) assessed in a Catphan phantom and a constant central absorbed dose. The required variations of CTDIvol(16) with respect to phantom size were analyzed in order to maintain each image quality index constant. The use of a fixed SD or CNR level leads to major dose ratios between extreme patient sizes (factor 22.7 to 44 for SD, 31.7 to 51.5 for CNR(2.8%)), whereas fixed ND and rLCD result in acceptable dose ratios ranging between factors of 2.9 and 3.9 between extreme phantom diameters. For a 5-9 mm rLCD1(%), adjusted ND values range between -0.84 and -0.11 HU mGy(-1). Our data provide guidance on dose reduction on the basis of patient dimensions and the required rLCD (e.g., to get a constant 7 mm rLCD(1%) for abdominal diameters of 10, 13, 16, 20 and 25 cm, tube current-time product should be adjusted in order to obtain CTDIvol(16) values of 6.2, 7.2, 8.8, 11.6 and 17.7 mGy, respectively).

[CT exposure from pediatric MDCT: results from the 2007-2008 SFIPP/ISRN survey]. / Niveaux d'exposition en tomodensitométrie multicoupes pédiatrique: résultats de l'enquête dosimétrique SFIPP/IRSN 2007-2008.

PURPOSE: To evaluate current exposure levels from pediatric MDCT examinations in order to issue recommendations for the routine clinical practice that may be used for establishing future diagnostic reference levels (DRL). Materials and methods. A survey was conducted at hospital sites affiliated with the SFIPP (Société Francophone d'Imagerie Pédiatrique et Prénatale). Tube potential and volume computed tomography dose index (CTDI) vol. values were obtained for three age groups (1, 5 and 10 years) for typical scanning indications of eight anatomical regions. RESULTS: Twenty of 29 sites provided us with a copy of their protocols. All ages groups combined, 97% of protocols used a tension level < or =120 kVp. For age groups 1, 5 and 10 years respectively, the 75th percentiles of dose distributions were: 31, 39.5 and 49.5 mGy for the "head" protocol; 24, 22 and 24 mGy for "head and neck"; 11, 11, and 11 mGy for "paranasal sinuses"; 46, 71 and 87 mGy for "petrous bone"; 3, 3.5 and 5.5 mGy for "chest"; 2, 3 and 4 mGy for "low dose lung"; 4, 4.5 and 7 mGy for "abdomen-pelvis"; 7, 11 and 12 mGy for "bone". The inter-center discrepancy for doses were still high. CONCLUSION: This study provided an evaluation of current practices in reference centers for pediatric imaging and allowed readjustment of MDCT dose recommendations. It could help in the development of DRLS for pediatric MDCT.