Mortality in French people with polyhandicap/profound intellectual and multiple disabilities.

BACKGROUND: In recent decades, progress has been made in the care of people with polyhandicap/profound intellectual and multiple disabilities (PIMD) through a better understanding of the pathophysiology and the development of new care management and rehabilitation strategies adapted to these extreme pathologies. Although there is a lack of knowledge about the health status and care management of the oldest people, a better understanding of the natural course of life of people with polyhandicap/PIMD would consequently allow the optimisation of preventive and curative care management strategies. Few robust data on mortality and life expectancy have been documented for this population in France. Our aims are to estimate the median survival time and assess the factors associated with mortality in people with polyhandicap/PIMD receiving care in France. METHODS: This study included people with polyhandicap/PIMD, followed by the French national cohort 'Eval-PLH' since 2015. These individuals were included in specialised rehabilitation centres and residential institutions. The people included in the first wave of the cohort (2015-2016) were eligible for the present study. Vital status on 1 January 2022 (censoring date) was collected in two ways: (1) spontaneous reporting by the participating centre to the coordinating team and (2) systematic checking on the French national death platform. According to the vital status, survival was calculated in years from the date of birth to the date of death or from the date of birth to the censoring date. The factors associated with mortality were evaluated using the Cox proportional regression hazards model. RESULTS: Data from 780 individuals aged between 3 and 67 years were analysed. At the censoring date, 176 (22.6%) had died, and the mean survival was 52.8 years (95% confidence interval: 51.1-54.5). Mortality was significantly associated with a progressive aetiology, recurrent pulmonary infections, drug-resistant epilepsy and a higher number of medical devices. CONCLUSIONS: This study shows for the first time the survival and impact of factors associated with mortality in people with polyhandicap/PIMD in France.

Psychiatric advance directives facilitated by peer workers among people with mental illness: economic evaluation of a randomized controlled trial (DAiP study).

AIMS: We aimed to assess the cost-effectiveness of psychiatric advance directives (PAD) facilitated by peer workers (PW-PAD) in the management of patients with mental disorders in France. METHODS: In a prospective multicentre randomized controlled trial, we randomly assigned adults with a Diagnostic and Statistical Manual of Mental Disorders, fifth edition diagnosis of schizophrenia, bipolar I disorder or schizoaffective disorders, who were compulsorily hospitalized in the past 12 months, to either fill out a PAD form and meet a peer worker for facilitation or receive usual care. We assessed differences in societal costs in euros (€) and quality-adjusted life-years (QALYs) over a year-long follow-up to estimate the incremental cost-effectiveness ratio of the PW-PAD strategy. We conducted multiple sensitivity analyses to assess the robustness of our results. RESULTS: Among the 394 randomized participants, 196 were assigned to the PW-PAD group and 198 to the control group. Psychiatric inpatient costs were lower in the PW-PAD group than the control group (relative risk, -0.22; 95% confidence interval, [-0.33 to -0.11]; P < 0.001), and 1-year cumulative savings were obtained for the PW-PAD group (mean difference, -€4,286 [-4,711 to -4,020]). Twelve months after PW-PAD implementation, we observed improved health utilities (difference, 0.040 [0.003-0.077]; P = 0.032). Three deaths occurred. QALYs were higher in the PW-PAD group (difference, 0.045 [0.040-0.046]). In all sensitivity analyses, taking into account sampling uncertainty and unit variable variation, PW-PAD was likely to remain a cost-effective use of resources. CONCLUSION: PW-PAD was strictly dominant, that is, less expensive and more effective compared with usual care for people living with mental illness.

Validation of a non-motor fluctuations questionnaire in Parkinson's disease.

INTRODUCTION: Non-motor fluctuations (NMF) in Parkinson's disease (PD) remain poorly recognized but have a high impact on patients' quality of life. The lack of assessment tools limits our understanding of NMF, compromising appropriate management. Our objective was to validate a hetero-questionnaire for NMF in PD patients at different stages of the disease: without treatment, without motor fluctuations, with motor fluctuations. METHODS: We included patients in 15 centers in France. Our questionnaire, NMF-Park, resulted from previous studies, allowing us to identify the more pertinent NMF for evaluation. Patients reported the presence (yes or no) of 22 selected NMF, and their link with dopaminergic medications. The assessment was repeated at one and two years to study the progression of NMF. We performed a metrological validation of our questionnaire. RESULTS: We included 255 patients (42 without treatment, 88 without motor fluctuations and 125 with motor fluctuations). After metrological validation, three dimensions of NMF were found: dysautonomic; cognitive; psychiatric. The sensory/pain dimension described in the literature was not statistically confirmed by our study. DISCUSSION: Our questionnaire was validated according to clinimetric standards, for different stages of PD. It was clinically coherent with three homogeneous dimensions. It highlighted a link between fatigue, visual accommodation disorder, and cognitive fluctuations; and the integration of sensory/pain fluctuations as part of dysautonomic fluctuations. It focused exclusively on NMF, which is interesting considering the described differences between non-motor and motor fluctuations. CONCLUSION: Our study validated a hetero-questionnaire of diagnosis for NMF for different stages of PD.

Nitrous oxide for pain management of first-trimester instrumental termination of pregnancy under local anaesthesia and/or minimal sedation: A systematic review and meta-analysis.

BACKGROUND: Inhalation of nitrous oxide and oxygen (N2O/O2) is used to reduce pain that is spontaneous or induced by procedures. N2O/O2 could be useful in the treatment of the pain in first-trimester termination of pregnancy performed under local anaesthesia and/or minimal sedation (FTOPL). OBJECTIVE: To evaluate the usefulness of N2O/O2 to reduce pain in FTOPL. SEARCH STRATEGY: Electronic databases including PubMed, Embase, and MEDLINE were searched using keywords. STUDY SELECTION: All studies comparing the use of N2O/O2 versus a placebo in the management of pain during FTOPL during the first trimester were included. Of the 199 studies identified, four were deemed eligible for this meta-analysis. DATA COLLECTION: The extracted results were perioperative pain, immediate and delayed postoperative pain, anxiety scores, and the secondary effects (nausea, vomiting). The data were analysed using Comprehensive Meta-Analysis software version 2.2.064. MAIN RESULTS: There was a significant difference in favour of N2O/O2 for perioperative pain (p = 0.006; SMD = - 0.31; 95 % CI, -0.54 - -0.09). No difference was found, however, in postoperative pain, nor was there a difference in the secondary effects (nausea, vomiting) (p = 0.61). A significant decrease in postoperative anxiety scores was seen in the pooled placebo group (p = 0.049; SMD = 0.41; and 95 % CI, 0.001-0.83). CONCLUSIONS: N2O/O2 reduces the pain of FTOPL. N2O/O2 could be recommended in FTOPL.

Altitude healing effect in severe asthmatic children.

BACKGROUND: The beneficial effect of a climatic treatment in children with asthma was established quite some time ago, but the mechanism of this beneficial effect has not been fully elucidated. We investigated the role of the cytokines of the TH2 pathway, reactive oxygen species (ROS) and reactive nitrogen species (RNS) over the course of a high-altitude climatic therapy. METHODS: A group of 67 children originating from various French towns suffering from uncontrolled severe asthma was sent via their medical specialists, to the Briançon climatic area. They were monitored over the course of an entire school year. During this time, they returned home for 15 days during the Christmas holidays. At each stage, assessment of asthma control, lung function examination (peak flow meter and spirometry), and measurement of exhaled NO, ROS and RNS in exhaled breath condensate (EBC), and the level of cytokines in the plasma of the TH2 pathway were carried out. RESULTS: The degree of asthma control improved at high altitude and worsened upon returning home. The average value of the peak expiratory flow also improved during the first 3 months but then worsened upon returning home, while the other spirometric parameters did not change. The level of expired NO and the scores for quality of life underwent a similar change. The level of RNS and ROS in the EBC did not change significantly. Besides, a marked and statistically significant decrease in the level of IL-13 and IL-10 was noted. CONCLUSION: The beneficial effect of a climatic stay of children suffering from allergic asthma at altitude appears to be linked with less allergenic stimulation.

Development and initial validation of the polyhandicap severity scale.

OBJECTIVES: Providing a new tool, based on the point of view of experts in polyhandicap, which assesses the global severity of the health status of polyhandicapped persons is necessary. We present herein the initial validation of the polyhandicap severity scale (PSS). METHODS: The initial development of the tool was undertaken in two steps: item selection and validation process. The final set included 10 items related to abilities and 17 items related to comorbidities and impairments. The patient selection criteria were as follows: age>3 years, age at onset of cerebral lesion under 3 years old, with a combination of motor deficiency and profound intellectual impairment, associated with restricted mobility and everyday life dependence. External validity, reproducibility (20 patients), responsiveness (38 patients), and acceptability were explored. RESULTS: During the 18-month study period, a total of 875 patients were included. Two scores were calculated: an abilities score and a comorbidities/impairments score (higher score, higher severity). The 2 scores were higher for: older patients, patients with a progressive etiology, patients with more devices and more medications, patients with higher dependency and lower mobility. Indicators of reproducibility and responsiveness were satisfactory. The mean time duration of fulfilling was 22minutes (standard deviation 5). CONCLUSIONS: Quantifying the health severity of polyhandicapped persons is necessary for both healthcare workers and health decision makers. The polyhandicap severity scale provides the first reliable and valid measure of the health severity status for children and adults.

Determinants of healthcare use by homeless people with schizophrenia or bipolar disorder: results from the French Housing First Study.

OBJECTIVES: There is limited evidence available on the health-seeking behaviours of individuals in relation to determinants of healthcare use. This study aimed to analyse the determinants of healthcare use (including both hospital and outpatient services) among homeless people with severe mental health illnesses. STUDY DESIGN: The study used data from a multicentre, randomised, controlled trial conducted in four large French cities (the French Housing First Study). METHODS: Data were drawn from 671 homeless people enrolled in the study between August 2011 and April 2014. Mobile mental health outreach teams recruited homeless individuals with severe mental health illnesses who were living on the street or in emergency shelters, hospitals or prisons. Data collection was performed during face-to-face interviews. Healthcare service use included hospitalisations, mental health and regular emergency department (ED) visits and outpatient visits to healthcare facilities or physicians' offices over a 6-month follow-up period. The data were analysed with zero-inflated (ZI) two-part models. RESULTS: In total, 61.1% of participants had at least one hospitalisation stay over the previous 6 months, with a mean of 25 (+/- 39.2) hospital days, and the majority (51%) had visited the ED (either for regular or mental health issues) during the same time period. The results confirmed the role of financial barriers (resources and health insurance) in seeking hospital care (P < 0.05). The main predictors for hospital use in the study population were a better social functioning score (odds ratio [OR]: 1.03; P < 0.001) and having schizophrenia (OR: 1.39; P < 0.01). Higher mental health scores (assessed by the Medical Outcomes Study 36-item Short Form Health Survey) (OR: 1.03, P < 0.01) and alcohol dependence (OR: 2.13; P < 0.01) were associated with not using ED healthcare services. Being 'absolutely homeless' predicted an increased use of the ED and a zero use of outpatient services. Inversely, no association with factors related to the homelessness trajectory was found in hospital ZI negative binomial models. CONCLUSION: This study is important because a comprehensive understanding of the determinants of healthcare use enables healthcare systems to adapt and develop. The efficiency of medicosocial interventions targeting the homeless population with mental health illnesses must also be assessed. CLINICAL TRIAL NUMBER: NCT01570712.

Health issues in polyhandicapped patients according to age: Results of a large French cross-sectional study.

INTRODUCTION: A better understanding of the natural course of the health status of patients with polyhandicap may optimize preventive and curative care management. From a large sample of patients aged from 3 to 25 years, we reported the description of their health status. METHODS: This was an 18-month cross-sectional study including patients aged from 3 to 25 years with a combination of severe motor deficiency and profound intellectual impairment. The patients were recruited from 4 specialized rehabilitation centers, 9 residential facilities, and a pediatric/neurological department. The following data were collected: polyhandicap etiology, health status (impairments, comorbidities, and neurodevelopmental status), medical devices, and rehabilitation procedures. RESULTS: A total of 545 patients were included (n=80 [3-5 years], n=166 [6-11 y], n=155 [12-17 y], and n=144 [18-25 y]). The etiology of polyhandicap was unknown for 11.5% of the cases. Behavioral disorders and (orthopedic and digestive) comorbidities were more frequent in the oldest age classes. The neurodevelopmental status of the patients was close to those of a 5- to 7-month-old child without progression across age. Gastrostomy was the most frequent device needed by the patients. DISCUSSION/CONCLUSION: Early detection and management of impairments and comorbidities may improve the disease course of the patients.

MICI-MINOTS: Linguistic and metric validation of a pediatric questionnaire on knowledge about inflammatory bowel disease.

BACKGROUND: Therapeutic education is an essential part of the treatment of chronic diseases, such as inflammatory bowel disease (IBD). The IBD-KID, developed in Canada in English, assesses children's and adolescents' acquired knowledge about their condition and has been validated in Canadian and Australian populations. However, there is no pediatric questionnaire in French to assess patients' knowledge about IBD. OBJECTIVE: To report the linguistic validation process and metric validity of the MICI-MINOTS, the French version of the IBD-KID. METHOD: The translation process consisted of three consecutive steps: forward-backward translation, acceptability testing, and cognitive interviews. The IBD-KID consists of 23 questions, but a 24th question about immunomodulatory therapy was added in the MICI-MINOTS. Psychometric testing was conducted with five groups: children with IBD, their parents, children in a control group, their parents, and health workers recruited from the Timone Pediatric Hospital and the Saint-Sébastien Maternal and Child Protection Center, Marseille, France. A total of 15 individuals completed the tool twice, with a 15-day interval. Internal consistency, reliability, external validity, reproducibility, and sensitivity to change were tested. RESULTS: A total of 38 children with IBD (sex: 20 boys, 18 girls; age: 13.90 [±2.88] years; 25 with Crohn's disease), 20 children in the control group, 58 parents (every child was included with one parent), and 62 health workers were included in the analysis. Intraclass correlation was 0.94 (95% confidence interval 0.83-0.98) for test-retest assessment. Readability using the Scolarius score corresponded to elementary school level. Among the children with IBD, 89.5% answered all 24 questions. For 23 questions, the mean score of children with IBD was higher than among children in the control group: 9.58 (±3.01) versus 5.47 (±3.56), respectively (P<0.01). Parents of children with IBD scored higher than parents of children in the control group: 10.63 (±3.16) versus 8.4 (±3.07), respectively (P=0.012). In the health workers' group, pediatric residents (17.82±3.46) scored higher than nurses 11.75 (±3.4) and ward clerks (8.67±2.40; P<0.01). Patients' knowledge score was significantly related to their parents' knowledge score (r=0.402, P=0.012) for 23 questions. CONCLUSION: The French version of the IBD-KID showed satisfactory psychometric properties to assess knowledge about the disease in French-speaking children.

Risk factors of exocrine and endocrine pancreatic insufficiency after pancreatic resection: A multi-center prospective study.

Management of functional consequences after pancreatic resection has become a new therapeutic challenge. The goal of our study is to evaluate the risk factors for exocrine (ExoPI) and endocrine (EndoPI) pancreatic insufficiency after pancreatic surgery and to establish a predictive model for their onset. PATIENTS AND METHODS: Between January 1, 2014 and June 19, 2015, 91 consecutive patients undergoing pancreatoduodenectomy (PD) or left pancreatectomy (LP) (72% and 28%, respectively) were followed prospectively. ExoPI was defined as fecal elastase content<200µg per gram of feces while EndoPI was defined as fasting glucose>126mg/dL or aggravation of preexisting diabetes. The volume of residual pancreas was measured according to the same principles as liver volumetry. RESULTS: The ExoPI and EndoPI rates at 6 months were 75.9% and 30.8%, respectively. The rate of ExoPI after PD was statistically significantly higher than after LP (98% vs. 21%; P<0.001), while the rate of EndoPI was lower after PD vs. LP, but this difference did not reach statistical significance (28% vs. 38.5%; P=0.412). There was no statistically significant difference in ExoPI found between pancreatico-gastrostomy (PG) and pancreatico-jejunostomy (PJ) (100% vs. 98%; P=1.000). Remnant pancreatic volume less than 39.5% was predictive of ExoPI. CONCLUSION: ExoPI occurs quasi-systematically after PD irrespective of the reconstruction scheme. The rate of EndoPI did not differ between PD and LP.

Can point-of-care ultrasound predict spinal hypotension during caesarean section? A prospective observational study.

Spinal anaesthesia for elective caesarean section is associated with maternal hypotension, secondary to alteration of sympathetic tone and hypovolemia, in up to 70% of cases. Measurement of the subaortic variation in the velocity time integral (VTI) after passive leg raising allows prediction of fluid responsiveness. Our objective, in this prospective single-centre observational study, was to assess the ability of change in VTI after 45° passive leg raising to predict hypotension after spinal anaesthesia. Ultrasound measurements were performed just before elective caesarean section. Anaesthesia, intravenous coloading and prophylactic vasopressor treatment were standardised according to current guidelines. We studied 40 women. Hypotension occurred in 17 (45%) women. The area (95%CI) under the receiver operating characteristics (ROC) curve for the prediction of spinal hypotension was 0.8 (0.6-0.9; p = 0.0001). Seventeen women had a change in VTI with leg elevation ≤ 8%, which was predictive for not developing hypotension, and 11 had a change ≥ 21%, predictive for hypotension. The grey zone between 8% and 21%, with inconclusive values, included 12 women. We suggest that cardiac ultrasound provides characterisation of the risk of hypotension following spinal anaesthesia at elective caesarean section, and therefore may allow individualised strategies for prevention and management.

Survival of melanoma patients treated with targeted therapy and immunotherapy after systematic upfront control of brain metastases by radiosurgery.

BACKGROUND: Targeted therapy (TT) and immunotherapies (ITs) have dramatically improved survival in metastatic melanoma (MM). However, their efficacy on brain metastasis (BM) remains limited and poorly documented. PATIENTS AND METHODS: Retrospective cohort of consecutive MM patients (pts) with BMs, all systematically upfront treated by Gamma-Knife (GK) at first BM and retreated in case of new BMs, from 2010 to 2015 at the time when ipilimumab BRAF ± MEK inhibitors and anti-PD1 were introduced in practice. Survival after 1st GK (OSGK1) according to prognostic factors and treatment. RESULTS: Among 179 consecutive pts treated by GK, 109 received IT and/or TT after the 1st GK. Median OSGK1 was 10.95 months and 1- and 2-year survival rates were 49.5% and 27.4%, respectively, versus a median overall survival (OS) of 2.29 months (p < .001) in those who did not receive IT or TT. In pts who initially had a single BM, median OS and 1- and 2-year survival rates were 14.46 months, 66.7% and 43.4%, respectively; in pts with 2-3 BMs: 8.85 months, 46.4% and 31%, respectively; in pts with >3 BMs: 7.25 months, 37.2% and 11.9%, respectively. Multivariate analysis for OSGK1 confirmed that IT and TT were significantly and highly protective. Best OSGK1 was observed in BRAF-wild-type pts receiving anti-PD1 or in BRAF-mutated pts receiving BRAF-inhibitors and anti-PD1 (12.26 and 14.82 months, respectively). CONCLUSION: In real-life MM pts with BMs, a strategy aiming at controlling BM with GK together with TT and/or TT seems to achieve unprecedented survival rates.

[Can the rate of episiotomy still be lowered? Status update in PACA region (south of France)]. / Peut-on encore diminuer le taux d'épisiotomie ? État des lieux en région PACA.

OBJECTIVE: To evaluate professional practices relative to episiotomies in the Provence Alpes Côte d'Azur (PACA) region by analysing their incidence in maternity hospitals, by type and by sector of activity. Following this, to analyse maternal and obstetric characteristics associated with episiotomies and the occurrence of perineal tears in Marseille's university hospitals (CHU). METHODS: Data were extracted from the database for the period from 1st January 2012 to 31 December 2014. The sample included 41 maternity hospitals: 13 private and 28 public. Twenty of the maternity hospitals were level 1, 15 were level 2, and 2 were level 3 (Nice and AP-HM). RESULTS: In the PACA region, 176,573 patients gave birth by vaginal delivery. The incidence of episiotomy over the 3 years was 21.6% (0.50% - 76.13%) with a statistically significant reduction in the incidence between 2012 and 2014 (P<0.001). There was a significant difference by sector (P<0.001) and level (P<0.001) of maternity hospitals. In the Marseille CHU, 21.6% of women had an episiotomy (66.4% in primiparas - 33.6% in multiparous) and 43% had perineal tears (62.3% in primiparas - 37.7% in multiparous). After multivariate analysis, gender, weight of the newborn, presentation, gestational age, and mode of delivery were shown to be factors significantly associated with occurrence of episiotomy and occurrence of perineal tear (P<0.001). CONCLUSION: A significant decrease in the incidence of episiotomy was observed in the PACA region from 2012 to 2014, associated with a wide variation in rates depending on the maternity hospitals, their types and their sectors.

Morphological Analysis of Healthy Aortic Arch.

OBJECTIVE/BACKGROUND: This study aimed to describe an arch morphology protocol in a healthy population, and to assess the impact of age and sex. METHODS: A retrospective morphology evaluation was conducted in a population with no personal history of thoracic aorta surgery or pathology, through computed tomography (CT) imaging analysis, using a standardised protocol. Based on centreline three dimensional coordinates, a single investigator calculated a series of parameters in the arch zones and in the total arch, using Matlab scripts. These were categorized as: (i) morphometric data: diameter, length and aortic angle of each zone, total arch angle, and length; (ii) geometric data: tortuosity index (TI), arch width, assimilated curvature radius (CRi), and attachment zone angles. Student or Mann-Whitney tests were used to compare parameter means. Their variability with age and sex was assessed through univariate and multivariate regression analysis. RESULTS: CT images from 123 subjects (mean ± SD age 53 ± 19 years) were reviewed. Significant correlation between age and morphology was found. The aorta expanded homogeneously and stretched heterogeneously with age because of posterior arch elongation. TI decrease, CRi, and attachment zone angle increase were also observed with aging. Age remained significantly associated with these morphological parameters, independently of body surface area and hypertension. Sex also affected morphology: longer total arch length and higher CRarch in men; lower zone 3 attachment angle in women CONCLUSION: Using mathematical algorithms, and with a view to improving endovascular arch treatment, this study provides a standardised arch morphology protocol and objectively identifies both age related evolution and sex related variation in the different zones.

Use of 3D orbital reconstruction in the assessment of orbital sexual dimorphism and its pathological consequences.

INTRODUCTION: Surrounded by a variety of structures including the facial sinuses and the brain, the human orbit displays unique anatomical features. It is known that orbital volume correlates with age and sex. The aim of this study was to evaluate sexual dimorphism of orbital volume relative to the size of the skull, and to establish criteria for gender determination. METHODS: Orbital volume was measured from 3D models of the orbits. The volumes were expressed in relation to the centroid size of the skull, to ensure that any sexual dimorphism in orbital volume was not simply due to a difference in skull size. Thirty-three male and 42 female subjects were included in the study. RESULTS: The volume of both orbits were significantly higher in men than in women (P=0.0001). The right, left and total orbital volumes relative to the centroid skull size were also significantly higher in men than women (P<0.05). The method was repeatable and reproducible. A test of gender determination was developed, with a precision of 77.3%. DISCUSSION: This is the first study showing a sexual dimorphism in orbital volume relative to skull size. This difference in volume could explain the greater predisposition to myopia in women and their more frequent need for orbital decompression in thyroid orbitopathies.

Cytogenetics and outcome of allogeneic transplantation in first remission of acute myeloid leukemia: the French pediatric experience.

We analyzed the impact of cytogenetics on 193 children enrolled in two successive French trials (LAME89/91 and ELAM02), who received hematopoietic stem cell transplantation during CR1. Detailed karyotype was available for 66/74 (89%) in LAME89/91 and 118/119 (99%) in ELAM02. Several karyotype and transplant characteristics differed according to therapeutic protocol: unfavorable karyotypes were more frequent in ELAM02 (36% vs 18%), pretransplant chemotherapy included high-dose cytarabine in ELAM02 and not in LAME89/91, IV replaced oral busulfan in the conditioning regimen, methotrexate was removed from post-transplant immunosuppression, and matched unrelated donor and cord blood transplantation were introduced. Five-year overall survival (OS) was 78.2% in LAME89 and 81.4% in ELAM02. OS was significantly lower for the unfavorable cytogenetic risk group in LAME89/91 when compared with intermediate and favorable groups (50% vs 90.6 and 86.4%, P=0.001). This difference was no longer apparent in ELAM02 (80.9% vs 71.3% and 5/5, respectively). Survival improvement for children with unfavorable karyotype was statistically significant (P=0.026) and was due to decrease in relapse risk. Five-year transplantation-related mortality was 6.75% in LAME89/91. In ELAM02, it was 3.2% for patients with a sibling donor and 10.9% with an unrelated donor or cord blood. We conclude that the outcome of children with unfavorable karyotype transplanted in CR1 has improved.

Learning curve for endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) of pancreatic lesions in a novel ex-vivo simulation model.

Background: Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) is essential in the management of digestive cancers. However, teaching and learning this technique remain challenging due to the lack of cost-effective models. Material and methods: This was a prospective experimental study using a complete porcine upper gastrointestinal ex-vivo organ package, placed in an Erlangen Active Simulator for Interventional Endoscopy (EASIE-R), and prepared with one cyst and two solid masses (2 cm). Five fellows inexperienced in EUS-FNA were enrolled, performing 10 procedures on each lesion, alternatively. The total time, number of attempts for success, of needle view losses, and of scope handling were recorded, associated with an independent skills rating by procedure. We compared the first 15 procedures with the last 15 for each fellow. Results: The fellows successfully performed all procedures in 2 to 40 minutes, requiring 1 to 6 attempts. All (5/5) improved their total time taken (P < 0.001), number of times when the EUS view of the needle was lost (P < 0.05), scope handling (P < 0.005), and skills rating (P < 0.001), whereas 4/5 (80 %) improved their number of attempts. The overall evaluation showed a significant decrease (P < 0.001) in the total time taken (11.2 ±â€Š7.8 vs 4.3 ±â€Š2.2 minutes), number of attempts (2.6 ±â€Š1.2 vs 1.2 ±â€Š0.7), number of times when the EUS view of the needle was lost (2.3 ±â€Š2 vs 0.5 ±â€Š0.7), and need for scope handling (1.1 ±â€Š1.7 vs 0.1 ±â€Š0.2). We also observed an improvement in skills rating (5 ±â€Š1.9 vs. 7.7 ±â€Š1.1). Conclusion: This newly designed ex-vivo model seems to be an effective way to improve the initial learning of EUS-FNA, by performing 30 procedures.

Risk Factor Analysis for the Mal-Positioning of Thoracic Aortic Stent Grafts.

OBJECTIVE: The present study aimed at quantifying mal-positioning during thoracic endovascular aortic repair and analysing the extent to which anatomical factors influence the exact stent graft positioning. METHODS: A retrospective review was conducted of patients treated between 2007 and 2014 with a stent graft for whom proximal landing zones (LZ) could be precisely located by anatomical fixed landmarks, that is LZ 1, 2, or 3. The study included 66 patients (54 men; mean age 51 years, range 17-83 years) treated for traumatic aortic rupture (n = 27), type B aortic dissection (n = 21), thoracic aortic aneurysm (n = 8), penetrating aortic ulcer (n = 5), intramural hematoma (n = 1), and floating aortic thrombus (n = 4). Pharmacologic hemodynamic control was systematically obtained during stent graft deployment. Pre- and post-operative computed tomographic angiography was reviewed to quantify the distance between planned and achieved LZ and to analyze different anatomical factors: iliac diameter, calcification degree, aortic angulation at the proximal deployment zone, and tortuosity index (TI). RESULTS: Primary endoleak was noted in seven cases (10%): five type I (7%) and two type II (3%). Over a mean 35 month follow up (range 3-95 months), secondary endoleak was detected in two patients (3%), both type I, and stent graft migration was seen in three patients. Mal-positioning varied from 2 to 15 mm. A cutoff value of 11 mm was identified as an adverse event risk. Univariate analysis showed that TI and LZ were significantly associated with mal-positioning (p = .01, p = .04 respectively), and that aortic angulation tends to reach significance (p = .08). No influence of deployment mechanism (p = .50) or stent graft generation (p = .71) or access-related factors was observed. Multivariate analysis identified TI as the unique independent risk factor of mal-positioning (OR 241, 95% CI 1-6,149, p = .05). A TI >1.68 was optimal for inaccurate deployment prediction. CONCLUSION: TI calculation can be useful to anticipate difficulties during stent graft deployment and to reduce mal-positioning.

[Oncogenic drivers in daily practice improve overall survival in patients with lung adenocarcinoma]. / Bénéfice à l'évaluation moléculaire en routine pour les cancers bronchiques métastatiques.

BACKGROUND: EGFR tyrosine kinase inhibitors and crizotinib are nowadays the optimal treatment for metastatic lung cancer with activation of EGFR mutations and ALK rearrangement. In addition, several targeted agents are in development for lung cancer with other oncodrivers. In France, since 2011, six oncodrivers are routinely tested in patients with stage IV. The aim of this study was to assess whether systematic detection of oncodrivers and matched targeted therapy improve overall survival in patients with advanced lung adenocarcinoma. METHODS: This study included all consecutive patients treated in our department for advanced lung adenocarcinoma from January 2012 to December 2013. We studied the impact in survival according to the presence of the driver and the targeted therapy. RESULTS: Among the 261 patients included, oncodrivers alterations were found in 43.5% of patients: EML4-ALK fusion genes (2.1%), EGFR (10.3%), KRAS (27.7%), BRAF (2.5%), HER2 (0.8%), and PI3KCA (0.8%) mutations. Twenty-nine percent of patients (n=32) with oncodrivers received matched targeted therapy. Patient treated by targeted agent appropriate to an oncogenic driver had a median survival of 21.1 months (95% CI: 14.7-27.5). The patients (n=79) who did not receive targeted therapy had a median survival of 6.6 months (95% CI: 4.3-8.9). The patients (n=150) without identified driver had a median survival of 9.7 months (95% CI: 6.7-11.7); P<0.001. CONCLUSION: An actionable oncodriver was routinely detected in nearly half of patients with advanced lung adenocarcinoma. This systematic detection may influence treatment outcomes, notably with matched targeted therapy.