[Health status and quality of life in ß-thalassemia adults in Marseille, France]. / État de santé et qualité de vie des patients ß-thalassémiques adultes à Marseille, France.

INTRODUCTION: The life expectancy of ß-thalassemia patients has increased over the last 20 years. In this study, we evaluated the current health status and quality of life of these patients managed in a reference center in Marseille. METHODS: This is a single-center, descriptive study conducted between June and August 2019 in patients over 18 years of age with ß-thalassemia major or intermedia. Clinical and paraclinical data were collected retrospectively and the SF-36 health survey questionnaire was proposed to each patient. RESULTS: 43 of 64 selected patients were included and divided into 2 groups: 35 patients with transfusion-dependent ß-thalassemia and 8 patients with non-transfusion-dependent ß-thalassemia. Liver iron overload is the most frequent complication, present in 80% of transfusion-dependent and 62.5% of non-transfusion-dependent patients. Cardiac iron overload is present only in the transfusion dependent ß-thalassemia group (20%). Hypogonadotropic hypogonadism remains the most common endocrine disorder (41.9%) followed by osteoporosis (37.2%). Among the 31 patients who completed the SF-36 questionnaire, physical and mental quality of life scores were lowered in transfusion dependent (respectively 42.7 and 46.8) as in non-transfusion-dependent patients (respectively 43.8 and 28.9). CONCLUSION: Despite an improvement in medical care, our patients with ß-thalassemia show an alteration in their quality of life that will need to be characterized in the entire French cohort.

Laparoscopic transperitoneal hernia repair (TAPP) in emergency: long-term follow-up in a high volume centre.

PURPOSE: Aim of this study was to analyse feasibility, safety and effectiveness of laparoscopic transperitoneal hernia repair (TAPP) approach to inguinal hernias in the emergency setting, with a longer follow-up than the studies present in literature. METHODS: We retrospectively analysed all patients who underwent emergency TAPP hernia repair in San Marco Hospital (Zingonia, Italy), from September 2010 to June 2020. A prospectively collected database of 685 consecutive TAPP hernia repair was reviewed. Feasibility and safety were evaluated through operative time, conversion rate, perioperative mortality, morbidity and prosthesis infection rate. Effectiveness was assessed by recurrence and complication rate, acute (during admission) and chronic (during follow-up) pain by Visual Analogic Scale (VAS), and recovery to normal activity in a long-term follow-up (mean period 1718 days). RESULTS: The final study group included 47 patients. The mean age was 59.6 years (range 22-89), 29 patients were male and 18 were female. The mean operation time was 64 min. Two cases were converted to open approach (4%). In four cases bowel resection became necessary (8.5%). Appendicectomy and omentectomy occurred once and twice, respectively (2% and 4%), and orchiectomy was required in two patients (4%). Seroma was the only postoperative complication that we registered in four patients. During a mean follow-up period of 1718 days, there was no recurrence of the hernia or other complications. Five patients referred mild occasional groin pain (VAS < 3), with quick relief without taking any pain killers. CONCLUSION: TAPP approach is a safe, feasible and effective therapeutic option for groin hernias in emergency setting. No recurrence or severe complications were reported in over 4 years of follow-up.

More accurate cancer-related excess mortality through correcting background mortality for extra variables.

Relative survival methods used to estimate the excess mortality of cancer patients rely on the background (or expected) mortality derived from general population life tables. These methods are based on splitting the observed mortality into the excess mortality and the background mortality. By assuming a regression model for the excess mortality, usually a Cox-type model, one may investigate the effects of certain covariates on the excess mortality. Some covariates are cancer-specific whereas others are variables that may influence the background mortality as well. The latter should be taken into account in the background mortality to avoid biases in estimating their effects on the excess mortality. Unfortunately, the available life table might not include such variables and, consequently, might provide inaccurate values of the background mortality. We propose a model that uses multiplicative parameters to correct potentially inaccurate background mortality. The model can be seen as an extension of the frequently used Estève model because we assume a Cox-type model for the excess mortality with a piecewise constant baseline function and introduce additional parameters that multiply the background mortality. The original and the extended model are compared, first in a simulation study, then in an application to colon cancer registry data.

[Same-eye comparison of pupillary dilation with an intraoperative standardized intracameral combination of mydriatics (Mydrane®) versus a preoperative ophthalmic (Mydriasert®) in standard cataract surgery in non-diabetic patients (French translation of the article)]. / Comparaison intra-individuelle de la dilatation pupillaire par une solution intracamérulaire standardisée combinée de mydriatiques (Mydrane®) en peropératoire versus un insert ophtalmique (Mydriasert®) en préopératoire dans la chirurgie de la cataracte standard de patients non diabétiques.

INTRODUCTION: Cataract surgery is the most commonly performed surgery in the world, and its success depends in part on the quality of mydriasis. PURPOSE: To compare, for the same eye, the pupillary dilation obtained with Mydrane® (standardized intracameral solution of 0.02% tropicamide, combined with 0.31% phenylephrine and 1% lidocaine) intraoperatively versus Mydriasert® (0.28mg tropicamide insert and 5.4mg phenylephrine) with a contact time between 45 and 60 minutes in the preoperative period. METHODS: Single center prospective study from November 2016 to January 2018 at the Laveran Army Instructional Hospital in Marseille. Patients referred for surgery were dilated at the preoperative consultation with Mydriasert®. The pupillary diameter after 45-60 minutes of contact with the insert was manually measured, by two different examiners, through the "iris image" tab of the Pentacam® elevation topography. Patients were dilated on the day of their cataract surgery with 0.2cc of Mydrane® injected in the anterior chamber through a paracentesis. Thirty seconds later, prior to injection of viscoelastic, an eye photograph was taken by screen capture. The pupillary diameter was evaluated by two different examiners with to the Piximeter 5.9 metrology software. The difference in pupil dilation between Mydriasert® and Mydrane® was tested with the paired series Student t-test. RESULTS: In total, 111 eyes of 82 patients were included. Mydriasert® achieved a mean pupillary dilation of 7.21±0.79mm. The mydriasis obtained with Mydrane® averaged 6.35±0.8mm. This difference of 0.86mm was statistically significant (P<0.001) with a confidence interval of 95% [-0.97; -0.74]. CONCLUSION: On average, Mydrane® dilates the pupil less than Mydriasert®. However, the mydriasis obtained with Mydrane® remains comfortable for the performance of the capsulorhexis. It helps save preoperative time and affords additional anesthetic to the cataract surgery. Nevertheless, the use of Mydriasert® is beneficial when extra mydriasis is required.

Saliva versus serum cortisol to identify subclinical hypercortisolism in adrenal incidentalomas: simplicity versus accuracy.

PURPOSE: Subclinical hypercortisolism (SCH) leads to metabolic derangements and increased cardiovascular risk. Cortisol autonomy is defined by the overnight 1 mg dexamethasone suppression test (DST). Saliva cortisol is an easier, stress-free, and cost-effective alternative to serum cortisol. We compared 23 h and post-1 mg DST saliva with serum cortisol to identify SCH in adrenal incidentalomas (AI). METHODS: We analyzed 359 DST obtained retrospectively from 226 AI subjects (173F/53 M; 19-83 years) for saliva and serum cortisol. We used three post-DST serum cortisol cutoffs to uncover SCH: 1.8, 2.5, and 5.0 µg/dL. We determined post-DST and 23 h saliva cortisol cutoffs by ROC curve analysis and calculated their sensitivities (S) and specificities (E). RESULTS: The sensitive 1.8 µg/dL cutoff defined 137 SCH and 180 non-functioning adenomas (NFA): post-DST and 23 h saliva cortisol S/E were: 75.2%/74.4% and 59.5%/65.9%, respectively. Using the specific 5.0 µg/dL cortisol cutoff (22 SCH/295 NFA), post-DST and 23 h saliva cortisol S/E were 86.4%/83.4% and 66.7%/80.4%, respectively. Using the intermediate 2.5 µg/dL cutoff (89 SCH/228 NFA), post-DST and 23 h saliva cortisol S/E were 80.9%/68.9% and 65.5%/62.8%, respectively. CONCLUSION: Saliva cortisol showed acceptable performance only with the 5.0 µg/dL cortisol cutoff, as in overt Cushing's syndrome. Lower cutoffs (1.8 and 2.5 µg/dL) that identify larger samples of patients with poor metabolic outcomes are less accurate for screening. These results may be attributed to pre-analytical factors and inherent patient conditions. Thus, saliva cortisol cannot replace serum cortisol to identify SCH among patients with AI for screening DST.

Same-eye comparison of pupillary dilation with an intraoperative standardized intracameral combination of mydriatics (Mydrane®) versus a preoperative ophthalmic (Mydriasert®) in standard cataract surgery in non-diabetic patients.

INTRODUCTION: Cataract surgery is the most commonly performed surgery in the world, and its success depends in part on the quality of mydriasis. PURPOSE: To compare, for the same eye, the pupillary dilation obtained with Mydrane® (standardized intracameral solution of 0.02% tropicamide, combined with 0.31% phenylephrine and 1% lidocaine) intraoperatively versus Mydriasert® (0.28mg tropicamide insert and 5.4mg phenylephrine) with a contact time between 45 and 60 minutes in the preoperative period. METHODS: Single center prospective study from November 2016 to January 2018 at the Laveran Army Instructional Hospital in Marseille. Patients referred for surgery were dilated at the preoperative consultation with Mydriasert®. The pupillary diameter after 45-60 minutes of contact with the insert was manually measured, by two different examiners, through the "iris image" tab of the Pentacam® elevation topography. Patients were dilated on the day of their cataract surgery with 0.2cc of Mydrane® injected in the anterior chamber through a paracentesis. Thirty seconds later, prior to injection of viscoelastic, an eye photograph was taken by screen capture. The pupillary diameter was evaluated by two different examiners with to the Piximeter 5.9 metrology software. The difference in pupil dilation between Mydriasert® and Mydrane® was tested with the paired series Student t-test. RESULTS: A hundred and eleven eyes of 82 patients were included. Mydriasert® achieved a mean pupillary dilation of 7.21±0.79mm. The mydriasis obtained with Mydrane® averaged 6.35±0.8mm. This difference of 0.86mm was statistically significant (P<0.001) with a confidence interval of 95% [-0.97; -0.74]. CONCLUSION: On average, Mydrane® dilates the pupil less than Mydriasert®. However, the mydriasis obtained with Mydrane® remains comfortable for the performance of the capsulorhexis. It helps save preoperative time and affords additional anesthetic to the cataract surgery. Nevertheless, the use of Mydriasert® is beneficial when extra mydriasis is required.

Goftte: A R package for assessing goodness-of-fit in proportional (sub) distributions hazards regression models.

BACKGROUND AND OBJECTIVE: In this paper, we introduce a new R package goftte for goodness-of-fit assessment based on cumulative sums of model residuals useful for checking key assumptions in the Cox regression and Fine and Gray regression models. METHODS: Monte-Carlo methods are used to approximate the null distribution of cumulative sums of model residuals. To limit the computational burden, the main routines used to approximate the null distributions are implemented in a parallel C++ programming environment. Numerical studies are carried out to evaluate the empirical type I error rates of the different testing procedures. The package and the documentation are available to users from CRAN R repositories. RESULTS: Results from simulation studies suggested that all statistical tests implemented in goftte yielded excellent control of the type I error rate even with modest sample sizes with high censoring rates. CONCLUSIONS: As compared to other R packages goftte provides new useful method for testing functionals, such as Anderson-Darling type test statistics for checking assumptions about proportional (sub-) distribution hazards. Approximations for the null distributions of test statistics have been validated through simulation experiments. Future releases will provide similar tools for checking model assumptions in multiplicative intensity models for recurrent data. The package may help to spread the use of recent advocated goodness-of-fit techniques in semiparametric regression for time-to-event data.

The carbonation kinetics of calcium hydroxide nanoparticles: A Boundary Nucleation and Growth description.

HYPOTHESIS: The reaction of Ca(OH)2 with CO2 to form CaCO3 (carbonation process) is of high interest for construction materials, environmental applications and art preservation. Here, the "Boundary Nucleation and Growth" model (BNGM) was adopted for the first time to consider the effect of the surface area of Ca(OH)2 nanoparticles on the carbonation kinetics. EXPERIMENTS: The carbonation of commercial and laboratory-prepared particles' dispersions was monitored by Fourier Transform Infrared Spectroscopy, and the BNGM was used to analyze the data. The contributions of nucleation and growth of CaCO3 were evaluated separately. FINDINGS: During carbonation the boundary regions of the Ca(OH)2 particles are densely populated with CaCO3 nuclei, and transform early with subsequent thickening of slab-like regions centered on the original boundaries. A BNGM limiting case equation was thus used to fit the kinetics, where the transformation rate decreases exponentially with time. The carbonation rate constants, activation energies, and linear growth rate were calculated. Particles with larger size and lower surface area show a decrease of the rate at which the non-nucleated grains between the boundaries transform, and an increase of the ending time of Ca(OH)2 transformation. The effect of temperature on the carbonation kinetics and on the CaCO3 polymorphs formation was evaluated.

Upper aerodigestive tract cancer and oral health status before radiotherapy: A cross-sectional study of 154 patients.

OBJECTIVES: We aimed to determine primarily the oral health status of patients with upper aerodigestive tract cancer before radiotherapy, and secondarily the prevalence of risk factors for poor oral status. METHODS: A cross-sectional study was conducted in Marseille University hospital. Assessment criteria were the Decay, Missing and Filled (DMF) Index and periodontal status. RESULTS: One hundred and fifty-four patients, mean age 60.9years, were included. The most common sites of primary tumors were the larynx (28.6%) and oral cavity (26.6%). Current or past smokers accounted for 80.5% of patients and 67% were alcohol abusers. Most patients (83.8%) did not have xerostomia. They ate three meals a day (61%), with sugar consumption in 40%. The median number of daily tooth brushings was 2, with a manual toothbrush (81.2%). Few patients used dental floss or interproximal brushes. Individual DMF index was 17.6 (D=2.3, M=9.3, F=6.0) and was higher in patients with xerostomia and alcohol abusers (P=0.01). Osseous level was 62.3% and 57.8% of patients had osseous infections, which were more common with poor hygiene (P=0.04). Most patients (85.7%) had periodontal disease, but incidence did not significantly differ according to risk factors. DISCUSSION: The DMF index was higher in presence of periodontal disease and osseous infections. Alcohol and xerostomia were associated with a high individual DMF index and osseous infections were more frequent in patients with poor hygiene. Patients with upper aerodigestive tract cancer are at high risk of osteoradionecrosis if they do not receive dental treatment before radiotherapy.

Laparoscopic pancreaticoduodenectomy for tumors of the head of pancreas; 10 cases for a single center experience.

OBJECTIVE: The tumors of the head of the pancreas are one of the leading causes of cancer-related death in Western countries. The current gold standard for these tumors is a Whipple procedure. This procedure did not change in its surgical steps since when it was initially introduced in 1935. More recently, a laparoscopic approach with similar outcomes has been described. The aim of this paper is to describe the laparoscopic surgical technique performed in our unit, reporting single center postoperative outcomes. PATIENTS AND METHODS: From the 1st January 2013 to the 31st December 2015 a database was created. Data about patients who underwent a laparoscopic pancreaticoduodenectomy (LPD) were collected prospectively. All patients were preoperatively assessed with blood samples, tumor markers, CT chest abdomen and pelvis and/or MRI pancreas. Only patients with specific characteristics were considered eligible for an LPD: performance status 0, body mass index (BMI) less than 30 kg/m2, a small neoplastic lesion (< 3.5 cm) confined to the pancreas, the absence of infiltrated organs and/or blood vessels (T1 or T2). Postoperative data and complications were recorded and described according to the Clavien-Dindo classification and the international study group of pancreatic surgery definitions. RESULTS: In a time interval of 36 months, 31 patients with an initially considered resectable pancreatic cancer were referred. 11 patients were found to have metastasis during the preoperative workout. Only 10 patients were considered eligible for a LPD. Six of them were men (60%). The mean BMI was 25.01 kg/m2 (19.6-29.8). 5 patients, who underwent to LPD did not have any comorbidities. An overall 50% of all patients were jaundice at the time of diagnosis with a mean bilirubin level of 181.3 µmol/L (119.7-307.8). All patients with a direct bilirubin greater than 250 µmol/L underwent a preoperative percutaneous biliary drainage. In the majority of the LPD performed (50%), the histology reported a pancreatic adenocarcinoma. Other postoperative histology described were: IPMN (20%), ampullar neoplasia (20%) and neuroendocrine tumor (10%). Neo-adjuvant chemotherapy was never considered indicated. The reported postoperative complications were: 1 anastomotic bleeding, 2 pancreatic fistula, 1 infected intra-abdominal collection and 1 delay gastric emptying. The pancreatic fistulas were considered grade A and grade B. One fatality after LPD occurred because of an uncontrollable, diffuse severe hemorrhagic gastritis associated with a GJ anastomosis bleeding in the POD 25. The mean hospital stay was 12.3 days (8-25). The mean operative time was 224 min (170-310). There were no intraoperative complications. The main intraoperative blood loss was 220 ml (180-400) and intraoperative blood transfusions were not required. The resection margins were negative (R0) in 100% of cases and the mean lymph nodes harvested were 24 (18-40). The LPD is still a not common practice. Our results are comparable with those reported in literature about the open technique. These remarkable surgical outcomes are probably related to the extremely careful preoperative patient selection performed. The indication for a laparoscopic vs. an open pancreaticoduodenectomy was based on a CT scan pancreas performed less than 30 days before the planned date of surgery and a careful preoperative assessment. A low complication rate and a relative short stay in hospital were associated to a good quality of life in the early postoperative period and an early referral for postoperative chemotherapy. Good clinical outcomes were associated with outstanding oncological results. CONCLUSIONS: Laparoscopic pancreaticoduodenectomy is a feasible surgical procedure. Remarkable oncological and surgical outcomes can be achieved with a morbidity and mortality rate in line with the data reported by the large series of open procedures.

Evaluation of hand hygiene compliance and associated factors with a radio-frequency-identification-based real-time continuous automated monitoring system.

BACKGROUND: Hand hygiene is a major means for preventing healthcare-associated infections. One critical point in understanding poor compliance is the lack of relevant markers used to monitor practices systematically. METHODS: This study analysed hand hygiene compliance and associated factors with a radio-frequency-identification-based real-time continuous automated monitoring system in an infectious disease ward with 17 single bedrooms. Healthcare workers (HCWs) were tracked while performing routine care over 171 days. A multi-level multi-variate logistics model was used for data analysis. The main outcome measures were hand disinfection before entering the bedroom (outside use) and before entering the patient care zone, defined as the zone surrounding the patient's bed (inside/bedside use). Variables analysed included HCWs' characteristics and behaviour, patients, room layouts, path chains and duration of HCWs' paths. FINDINGS: In total, 4629 paths with initial hand hygiene opportunities when entering the patient care zone were selected, of which 763 (16.5%), 285 (6.1%) and 3581 (77.4%) were associated with outside use, inside/bedside use and no use, respectively. Hand hygiene is caregiver-dependent. The shorter the duration of the HCW's path, the worse the bedside hand hygiene. Bedside hand hygiene is improved when one or two extra HCWs are present in the room. INTERPRETATION: Hand hygiene compliance at the bedside, as analysed using the continuous monitoring system, depended upon the HCW's occupation and personal behaviour, number of HCWs, time spent in the room and (potentially) dispenser location. Meal tray distribution was a possible factor in the case of failure to disinfect hands.

Prevalence of obstructive sleep apnoea syndrome following oropharyngeal cancer treatment: A prospective cohort study.

OBJECTIVES: To evaluate the prevalence of obstructive sleep apnoea syndrome (OSAS) in a population of patients treated for an advanced oropharyngeal cancer (AJCC Stage III or IV), depending on treatment strategy, and to evaluate its impact on quality of life. DESIGN: Prospective cohort study. SETTING: University Teaching Hospital of La Conception, Marseille, France. PARTICIPANTS: Fifty-one disease-free patients were included. Forty-one patients received a combined chemoradiotherapy, while 10 patients were treated by surgery followed by chemoradiotherapy. MAIN OUTCOME MEASURES: Every patient underwent a formal sleep consultation and was asked to complete the Epworth Sleepiness Scale and EORTC QLQ C-30 and the EORTC H&N 35 questionnaires. A home overnight respiratory polygraphy was performed in every subject. RESULTS: The mean time between the end of cancer treatment and the OSAS analysis was 54.04 months [20; 84]. An OSAS was found in 25.49% of our patients. There was no significant difference between patients treated with either surgery (30%) or CRT (24.39%), P=.79. The EORTC QLQ C-30 questionnaire showed a significant difference between positive and negative OSAS groups in the Global Health Status Scale (50.64 vs 67.11, P=.02) and in the fatigue item (35.04 vs 17.25, P=.03). CONCLUSIONS: Our population with advanced oropharyngeal cancer, whatever the treatment strategy it may be, was at risk of developing OSAS with negative impact on quality of life. A routine screening and treatment of OSAS seems necessary to improve the quality of life of patients treated for advanced oropharyngeal cancer.

Meta-analysis of major bleeding events on aspirin versus vitamin K antagonists in randomized trials.

BACKGROUND AND OBJECTIVES: The relative bleeding risk of aspirin versus vitamin K antagonists (VKA) is unclear. Most of previous meta-analyses included trials with target INR for VKA therapy far beyond usually recommended range (2-3). The aim of this study was to compare the bleeding risk of aspirin and VKA, as indicated by the aggregate body of clinical evidence including data from the recently published WARCEF trial. METHODS: In this meta-analysis we included randomized controlled trials that compared aspirin to VKA (1.4

[Oncological results of active surveillance in prostate cancer: A retrospective multicentric cohort]. / Résultats oncologiques de la surveillance active dans le cancer de la prostate : série rétrospective multicentrique.

PURPOSE: To report oncological outcomes of patients with prostate cancer undergoing active surveillance according to SURACAP criteria. METHODS: This multicentric study included patients who were initially treated with active surveillance for localized prostate cancer according to the SURACAP criteria. The duration of active surveillance as well as the causes of discontinuing the protocol and the definitive pathological results of patients who further underwent radical prostatectomy were retrospectively evaluated. The predictors of discontinuing active surveillance were assessed using a univariable Cox Model. In addition, the predictive value of initial MRI was assessed for patients who performed such imagery. RESULTS: Between 2007 and 2013, 80 patients were included, with a median age of 64 years [47-74]. Median follow-up was 52.9 months [24-108]. At 5 years follow-up, 43.4% patients were still under surveillance. Among patients that underwent surgery, 17.8% had an extra-capsular extension. The risk of discontinuing was not significantly greater for patients with tumor size of 2 or 3mm versus 1mm (HR=0.9 [0.46-1.75], P=0.763), 2 positives cores versus 1 (HR=0.98 [0.48-2.02], P=0.967), T2a vs. T1c stage (HR=2.18 [0.77-6.18], P=0.133), increased PSA level (HR=1 [0.96-1.15], P=0.975) or the patient's age (HR=1 [0.93-1.16], P=0.966). Among the 50 patients who performed initial MRI, the results of such imagery was not significantly associated to the risk of discontinuing active surveillance MRI (HR=1.49 [0.63-3.52], P=0.36). CONCLUSION: Although this study reveals a high rate of release from active surveillance at 5 years, the rate of extra-capsular tumors reported in the group of patients that underwent surgery is among the lowest in literature. LEVEL OF EVIDENCE: 4.

BLM germline and somatic PKMYT1 and AHCY mutations: Genetic variations beyond MYCN and prognosis in neuroblastoma.

Neuroblastoma (NB) is the most common extra cranial solid tumor of childhood and often lethal in childhood. Clinical and biologic characteristics that are independently prognostic of outcome in NB are currently used for risk stratification to optimally the therapy. It includes age at diagnosis, International Neuroblastoma Staging System tumor histopathology and MYCN amplification. However, even in patients with theoretically good prognosis, such as localized tumor and non-amplified MYCN, either disease progress or recurrence may occur. Potential genetic determinants of this unfavorable behavior are not yet fully clarified. The presence of elevated expression of AHCY, PKMYT1, and BLM has accompanied poor prognosis MYCN-amplified neuroblastoma patients. Considering the potential implication of these genes on the clinical management of NB, we hypothesize that the identification of genetic variations may have significant impact during development of the recurrent or progressive disease. Using targeted DNA sequencing, we analyzed the mutation profiles of the genes PKMYT1, AHCY, and BLM in tumor samples of five patients with MYCN amplified and 15 MYCN non-amplified NB. In our study, BLM germline variants were detected in two patients with MYCN-non-amplified neuroblastoma. Our data allow us to hypothesize that, regardless of MYCN status, these mutations partially abolish BLM protein activity by impairing its ATPase and helicase activities. BLM mutations are also clinically relevant because BLM plays an important role in DNA damage repair and the maintenance of genomic integrity. We also found a novel variant in our cohort, PKMYT1 mutation localized in the C-terminal domain with effect unknown on NB. We hypothesize that this variant may affect the catalytic activity of PKMYT1 in NB, specifically when CDK1 is complexed to cyclins. The prognostic value of this mutation must be further investigated. Another mutation identified was a nonsynonymous variant in AHCY. This variant may be related to the slow progression of the disease, even in more aggressive cases. It affects the maintenance of the catalytic capacity of AHCY, leading to the consequent functional effects observed in the NB patients studied. In conclusion, our hypothesis may provide that mutations in BLM, AHCY and PKMYT1 genes found in children with MYCN-amplified or MYCN-non amplified neuroblastomas, may be associated with the prognosis of the disease.

Challenges in the estimation of Net SURvival: The CENSUR working survival group.

BACKGROUND: Net survival, the survival probability that would be observed, in a hypothetical world, where the cancer of interest would be the only possible cause of death, is a key indicator in population-based cancer studies. Accounting for mortality due to other causes, it allows cross-country comparisons or trends analysis and provides a useful indicator for public health decision-making. The objective of this study was to show how the creation and formalization of a network comprising established research teams, which already had substantial and complementary experience in both cancer survival analysis and methodological development, make it possible to meet challenges and thus provide more adequate tools, to improve the quality and the comparability of cancer survival data, and to promote methodological transfers in areas of emerging interest. METHOD: The Challenges in the Estimation of Net SURvival (CENSUR) working survival group is composed of international researchers highly skilled in biostatistics, methodology, and epidemiology, from different research organizations in France, the United Kingdom, Italy, Slovenia, and Canada, and involved in French (FRANCIM) and European (EUROCARE) cancer registry networks. RESULTS: The expected advantages are an interdisciplinary, international, synergistic network capable of addressing problems in public health, for decision-makers at different levels; tools for those in charge of net survival analyses; a common methodology that makes unbiased cross-national comparisons of cancer survival feasible; transfer of methods for net survival estimations to other specific applications (clinical research, occupational epidemiology); and dissemination of results during an international training course. CONCLUSION: The formalization of the international CENSUR working survival group was motivated by a need felt by scientists conducting population-based cancer research to discuss, develop, and monitor implementation of a common methodology to analyze net survival in order to provide useful information for cancer control and cancer policy. A "team science" approach is necessary to address new challenges concerning the estimation of net survival.

Value of CMR in quantification of paravalvular aortic regurgitation after TAVI.

AIMS: To assess the value of cardiac magnetic resonance (CMR) using phase-contrast velocity mapping for paravalvular aortic regurgitation (PAR) quantification. METHODS AND RESULTS: All patients undergoing transcatheter aortic valve implantation (TAVI) in our centre between November 2012 and August 2013, without CMR-contraindication were included. PAR severity was assessed 5 days after TAVI using: transthoracic echocardiography (TTE) and CMR [regurgitant volume (RV), regurgitant fraction (RF)]. Aortic regurgitation (AR) index was obtained during TAVI. Thirty of 51 patients who underwent TAVI were included (COREVALVE, n = 10; or EDWARDS SAPIEN XT, n = 20). At TTE, PAR was mild in 22, moderate in 3, and severe in 5 patients. Reliable phase-contrast images were acquired at the sino-tubular junction for SAPIEN and at the tubular portion of the ascending aorta for COREVALVE. The reproducibility of CMR was high (coefficient of correlation = 0.99 for intra- and inter-operator variability). At CMR, RV, and RF were significantly (P < 0.0005) correlated with AR severity at TTE, with mean RF values at 9.2 ± 7.6% in mild, 20.3 ± 4.2% in moderate, and 46.8 ± 10.8% in severe PAR. A cut-off value of RF < 14% at CMR accurately discriminated mild from moderate/severe (sensitivity: 100%, specificity: 82%). The mean AR index was 29.4 ± 6 for mild and 13.8 ± 5 for moderate/severe PAR. Three patients had a RF > 14% and a low AR index <25 despite a mild PAR at TTE, suggesting an underestimation at TTE. CONCLUSION: CMR is a reproducible, accurate, and reliable method to assess PAR severity. CMR may allow correcting an underestimation at TTE when AR index is doubtful.