Search

Resume But de l’etude Le lien entre l’ileus postoperatoire, la duree de sejour et l’autonomie rapportee par le patient (ARP) n’est pas connu alors que cette ARP pourrait aider le chirurgien a adapter le jour de sortie du patient. Le but de cette etude etait d’evaluer l’evolution de l’ARP dans la periode postoperatoire, ainsi que les differents facteurs influencant cette evolution. Patients et methodes Cette etude retrospective sur une base de donnees prospective incluait les patients operes d’une chirurgie colorectale dans un seul centre sur une periode de 14 mois. L’ARP etait defini en utilisant la premiere partie du Groningen Activity Restriction Scale appele « activity of the daily life » (de 9 le meilleur) a 45 (le moins bon). Resultats Parmi les 101 patients operes, 80 % retrouvaient leur ARP preoperatoire (± 5 points) pendant 2 jours precedant la sortie. L’ARP etait significativement diminuee par la chirurgie (p 2 l’aggravait (p = 0,03). Les programmes de rehabilitation amelioree tendaient a ameliorer la recuperation de l’ARP (p = 0,09). Conclusion L’ARP pourrait etre utilisee pour optimiser le jour de sortie d’un patient apres chirurgie colorectale.

While so-called brown bodies were first defined in the 1950s as colorful aggregates of cells in the general cavity of echinoderms and other marine benthic taxa, their distribution and role have not yet been fully clarified. This work characterized free coelomocytes and corresponding aggregates ("bodies") in the hydrovascular system and perivisceral coelom, as well as those attached on the membranes of the viscera, in the holothuroid Cucumaria frondosa. Responses to the presence of foreign particles were investigated, providing novel insights on the immune system. A total of eight coelomocyte cell types was detected, while aggregates were formed of three to six types of coelomocytes. Only red-colored aggregates were found in the hydrovascular system, whereas brown aggregates were confined to the perivisceral coelom. The encapsulation mechanism of foreign particles injected in the hydrovascular system was monitored. Particles were first gathered by phagocytes and vibratile, crystal, and morula cells into a whitish aggregate that was then covered by hemocytes, imparting a red color to the aggregates. After their transfer to the perivisceral coelom, aggregates became brown and were ultimately expelled through the anus. Finally, a range of stressors (i.e., harvesting method, presence of a predator, and physical injury) was found to increase the abundance of aggregates, thus highlighting the role of these bodies in the immune response of C. frondosa.

Avoiding the use of nasogastric tubes (NGTs) is recommended after colorectal surgery but there is no consensus on intraoperative gastric decompression using NGTs during colorectal surgery. The objective was to assess the effect of avoiding insertion of NGTs during colorectal surgery for the recovery of gastrointestinal (GI) functions. 1561 patients undergoing colorectal surgery, for whom information on NGT use was available, were included in this retrospective analysis and propensity score analysis of the prospective GRACE Audit database. Patients who did and did not have an NGT during surgery were compared. Among the study population of 1561 patients, 696 patients were matched to correct baseline differences between groups. The no-NGT group significantly improved GI motility impairment (e.g., less postoperative nausea [OR = 0.59; CI 95%: 0.42–0.84] and a better tolerance of early feeding [OR = 2.07; CI 95%: 1.33–3.22]). Such an association was also highlighted for reduced postoperative morbidity [OR = 0.60; CI 95%: 0.43–0.83], and especially pulmonary complications [OR = 0.08; CI 95%: 0.01–0.59], or parietal complications [OR = 0.29; CI 95%: 0.09–0.87]. The risk of postoperative ileus was not significantly reduced in the no-NGT group [OR = 0.67; CI 95%: 0.43–1.06]. No NGT insertion during colorectal surgery is safe and could improve postoperative GI function recovery.

Purpose/background Quetiapine is a relatively new atypical antipsychotic with fewer adverse effects. It is increasingly prescribed to patients. The purpose of this study was to describe the cases of poisoning observed at the western France Poison Control Centre and identify potential risk factors that increase the severity of the cases. Methods This was a retrospective study of self-poisoning with quetiapine as reported by the western France Poison Control Centre between 2007 and 2017. Results There were 372 cases of quetiapine poisoning. Circumstances are known in 367 of 372 cases. There were 75 cases of null severity (grade 0), 133 cases of mild severity (grade 1), 85 cases of moderate severity (grade 2), and 79 cases of high severity (grade 3). Five deaths were listed in this series. The most commonly observed symptoms were neurological and cardiovascular in nature (drowsiness, coma, tachycardia, hypotension). Of these cases, 79.8% included voluntary ingestions. Among 302 cases with coagents, the most common coagents were benzodiazepines (56%), other psychotropic drugs (41%), and antidepressants (37%). An evaluated ingested dose 1500 mg or greater and 2 or more coagents increase the risk of severe poisoning. In particular, concomitant ingestion of benzodiazepines and antidepressants with quetiapine was associated with high severity (odds ratio, 2.478 [confidence interval, 1.3-4.723]; odds ratio, 1.820 [confidence interval, 1.010-3.316]). Conclusions Quetiapine may lead to severe poisoning for which there is currently no specific treatment. Patients and practitioners should be aware of this when quetiapine is prescribed, particularly when used in combination with other medications, and in order to deal with cases of poisoning.

The environmental control of reproductive processes is central to both fundamental and applied aspects of animal ecology. The present study experimentally assessed how environmental factors modulate gametogenesis and spawning and impact embryo development and survival in the holothuroid Cucumaria frondosa, a cold-water echinoderm with lecithotrophic development. Adults were exposed to three seawater temperatures, four photoperiod regimes, and two food concentrations during 120 days overlapping the natural gametogenic and spawning periods. Among all the treatments tested, exposure to ambient conditions of water temperature (−1 to 3 °C), photoperiod (8 to 13 h of light) and food concentration (3 × 103 ± 896 rotifers g−1 of sea cucumbers d−1) yielded the greatest reproductive output and embryo survival. At pre-spawning, males and females had the highest gonad index (~33%) and where filled with mature gametes. At spawning, females in ambient conditions released the highest number of oocytes (1.2 × 103 oocytes female−1) and yielded the highest embryo survival rates (21% at 20 days post fertilization). Individuals exposed to warmer water temperatures (6 and 12 °C) experienced delayed gametogenesis and did not spawn. Individuals under 24-h light, 24-h dark, and advanced (4 months) photoperiods showed delayed gametogenesis and low numbers of oocytes released; moreover, embryos died within 10 days post fertilization. Individuals fed with high food concentration (6 × 103 ± 982 rotifers g−1 of sea cucumbers d−1) showed similar results to ambient conditions, suggesting that increased food supply neither decreased nor enhanced reproductive output over the experimental period. This study sheds new light on the environmental drivers of reproductive success in C. frondosa, which is of value for developing conservation strategies and mariculture protocols in cold-water holothuroids with lecithotrophic development.

The present study investigated methods to trigger spawning and artificially induce oocyte maturation in the commercial cold-water suspension-feeding sea cucumber Cucumaria frondosa. Spawning occurred after exposure to live phytoplankton, commercial phytoplankton paste, and conspecific sperm. Live phytoplankton at 1 × 105 cells ml−1 induced the highest proportion of females to spawn (mean of 56%); promoted the greatest oocyte release (mean of 19,200 oocytes female−1), best quality of eggs and highest survival of embryos (65%; 20 d post fertilization). More concentrated live phytoplankton (1 × 106 cells ml−1) triggered 43% of the females to release ~16,100 oocytes female−1 and survival rates 20 d post fertilization were lower (50%). Both phytoplankton paste treatments (1 × 105 and 1 × 106 cells ml−1) yielded intermediate results in terms of percent spawning females (26%), abundance of oocytes released (11,000 and 7300 oocytes female−1, respectively), quality of eggs, and survival of embryos (44 and 50%, respectively). Sperm from conspecific (2 and 10 × 106 spermatozoa ml−1) induced the lowest proportion of females to spawn (16%) with release of 3000 and 1700 oocytes female−1, respectively; furthermore, all embryos died within 10 d post fertilization. Results for males were slightly different: spawning was more frequent (63%) in the sperm treatment at 2 × 106 spermatozoa ml−1 followed by live phytoplankton at 1 × 106 and 1 × 105 cells ml−1 (43%), and phytoplankton paste at 1 × 105 cells ml−1 (46%); the lowest spawning success was observed for phytoplankton paste at 1 × 106 cells ml−1 and conspecific sperm at 10 × 106 spermatozoa ml−1 (26%). Thermal shock, desiccation, potassium chloride (injection or bath), and serotonin (injection) did not induce spawning in C. frondosa. When oocytes isolated from mature ovaries were exposed to three different concentrations of 1-Methyladenine (1-MA), Dithiothreitol (DTT), 2,3-Dimercapto-1-propanol (BAL), and L-cysteine (L-cyst), DTT at 10−1 M induced the highest proportion of oocytes (48%) to shed follicle cells (i.e. ovulate); whereas other treatments induced only 2–6% of ovulation, similar to the control (seawater). All oocytes that shed follicle cells remained unfertilizable. Overall, live phytoplankton emerged as the most suitable spawning trigger for C. frondosa, a Dendrochirotida that produces maternally-provisioned oocytes. In the context of expanding sea cucumber aquaculture, this finding provides a tool to maximize the availability of gametes in this cold-water species, with possible applicability to similar commercial dendrochitotids.

International audience; Mostly studied at the individual level, the analysis of immigrants’ health status at a populational level may provide a different perspective to investigate, including social determinants as part of the explanation of the relationship between them and health status in France. We analyzed freely accessible databases curated by French public bodies. The dependent variables were death rate and mean age at death. Immigrant rate and covariates associated with either of the outcomes were explored in univariate and multivariate models. Linear models were used to explain the mean age at death, whereas tobit models were used to explain the death rate. The immigrant rate varied markedly from one department to another, as did healthcare accessibility, population’s age profile, and economic covariates. Considering univariate models, almost all the studied covariates were significantly associated with comes. The immigrant rate was associated with a lower death rate and a lower age at death. In multivariate models, the immigrant rate was no longer associated with age at death but was still negatively associated with the death rate. In France, the departments with a higher proportion of immigrants were those with a lower death rate, possibly because immigrants are attracted to economically thriving areas.

International audience; Objectives: The impact of conventional treatment for acute myeloid leukemia (AML) on the nutritional, cognitive, and functional status of elderly patients is seldom studied. This assessment was performed in the context of the LAMSA 2007 trial.Methods: The trial enrolled 424 patients with de novo AML. Among them, 316 benefited from geriatric assessment (GA) including nutritional, cognitive, and functional status and were scored according to Eastern Cooperative Oncology Group (ECOG) and sorror for the prediction of treatment toxicity, morbidity, and mortality. Patients were investigated at diagnosis for three times during follow-up.Results: This study showed that AML and its treatment have no impact on cognitive (P = .554) nor functional status (P = .842 for Activity of Daily Living and P = .087 for Instrumental Activities of Daily Living). The nutritional status improved over time (P = .041). None of these three parameters at baseline, associated or not with ECOG and sorror scores, impacted survivals or toxicities.Conclusions: The cognitive, functional, and nutritional status had no impact in this cohort of fit elderly AML patients without unfavorable cytogenetics. The GA tools used provided no additional information compared with ECOG and sorror scores, to predict toxicity, morbidity, or mortality due to intensive chemotherapy.

Recent efforts have been devoted to the link between responses to non-physical stressors and immune states in animals, mostly using human and other vertebrate models. Despite evolutionary relevance, comparatively limited work on the appraisal of predation risk and aspects of cognitive ecology and ecoimmunology has been carried out in non-chordate animals. The present study explored the capacity of holothuroid echinoderms to display an immune response to both reactive and anticipatory predatory stressors. Experimental trials and a mix of behavioural, cellular and hormonal markers were used, with a focus on coelomocytes (analogues of mammalian leukocytes), which are the main components of the echinoderm innate immunity. Findings suggest that holothuroids can not only appraise threatening cues (i.e. scent of a predator or alarm signals from injured conspecifics) but prepare themselves immunologically, presumably to cope more efficiently with potential future injuries. The responses share features with recently defined central emotional states and wane after prolonged stress in a manner akin to habituation, which are traits that have rarely been shown in non-vertebrates, and never in echinoderms. Because echinoderms sit alongside chordates in the deuterostome clade, such findings offer unique insights into the adaptive value and evolution of stress responses in animals.

IntroductionIn the context of the COVID-19 pandemic, early identification of patients who are likely to get worse is a major concern. Severity mainly depends on the development of acute respiratory distress syndrome (ARDS) with a predominance of subpleural lesions. Lung point-of-care ultrasonography (L-POCUS) is highly effective in detecting pulmonary peripheral patterns and may be appropriate for examining patients with COVID-19. We suggest that L-POCUS performed during the initial examination may identify patients with COVID-19 who are at a high risk of complicated treatment or unfavourable evolution.Methods and analysisPoint-of-care ultrasonography for risk stratification of non-critical COVID-19 patients on admission is a prospective, multicentre study. Adult patients visiting the emergency department (ED) of participating centres for suspected or confirmed COVID-19 are assessed for inclusion. Included patients have L-POCUS performed within 48 hours following ED admission. The severity of lung damage is assessed using the L-POCUS score based on 36 points for ARDS. Apart from the L-POCUS score assessment, patients are treated as recommended by the WHO. For hospitalised patients, a second L-POCUS is performed at day 5±3. A follow-up is carried out on day 14, and the patient’s status according to the Ordinal Scale for Clinical Improvement for COVID-19 from the WHO is recorded.The primary outcome is the rate of patients requiring intubation or who are dead from any cause during the 14 days following inclusion. We will determine the area under the ROC curve of L-POCUS.Ethics and disseminationThe protocol has been approved by the French and Belgian Ethics Committees and is carried out in accordance with the Declaration of Helsinki and Good Clinical Practice guidelines. The study is funding by a grant from the French Health Ministry, and its findings will be disseminated in peer-reviewed journals and at scientific conferences.Trial registration numberNCT04338100.

The objective was to develop a radiological score obtained from multi-detector computed tomography (MDCT) to differentiate between single band adhesion (SBA) and matted adhesions (MA) as the etiology of small bowel obstruction (SBO). All consecutive patients who underwent surgery from January 2013 to June 2018 for adhesion-induced SBO were retrospectively included. Among the 193 patients having surgery for SBO, 119 (61.6%) had SBA and 74 (38.4%) had MA surgically proven. In multivariate analysis, the presence of a beak sign (OR = 3.47, CI [1.26; 9.53], p = 0.02), a closed loop (OR = 11.37, CI [1.84; 70.39], p = 0.009), focal mesenteric haziness (OR = 3.71, CI [1.33; 10.34], p = 0.01) and focal and diffuse peritoneal fluid (OR = 4.30, CI [1.45; 12.73], p = 0.009 and OR = 6.34, CI [1.77; 22.59], p = 0.004, respectively) were significantly associated with SBA. Conversely, the presence of diffuse mesenteric fluid without focal fluid (OR = 0.23, CI [0.06; 0.92], p = 0.04) and an increase of the diameter of the most dilated loop (OR = 0.94, CI [0.90; 0.99], p = 0.02) were inversely associated with SBA. Using the significant predictive factors of SBA, we built a composite score to radiologically predict the etiology of SBO. The area under the receiver operating characteristic (ROC) curve of the score was 0.8274. For a cut-off score of -0.523, sensitivity, specificity and the percentage of patients correctly classified were 78.4%, 84.6% and 80%, respectively. If the score is ≥ 7, the probability that the mechanism of SBO is not SBA was 100%. The present score, validated in a different population, could be a significant tool in the decision for surgical management.

International audience

Background Students’ choice of medical specialties has evolved throughout year, with a growing interest in quality of life and in technological specialties. We investigated the repartition of such choices in the world and its influencing factors with a focus on the gender's influence, for helping policy-makers to deal with medical shortage and territorial to specialty disconnect. Methods A systematic search was conducted on MEDLINE and Scopus from January 2010 to January 2020. Data extraction and analysis followed JBI and PRISMA recommendations. The selected articles had to focus on medical students, detail their choice of specialty, and look for factors influencing their choice. Articles were excluded if they only assessed the attractiveness of a specialty, or evaluated a public policy. This review was registered on PROSPERO, CRD 42020169227. Findings 751 studies were screened, and fifty-four were included. Surgery and internal medicine were the most wanted specialties, both in occidental and non-occidental countries. The main factors influencing the choice of specialty were lifestyle, work-life balance and discipline interest, with variation across different countries. Gender clearly affected this choice with 63.7% of men willing radiology and 14.7% of men in obstetrics and gynecology. Interpretation Influential factors vary with specialty and are affected by the country of residence. Gender has a great impact in students’ willingness to work in specific specialties. Policymakers should adapt their appealing strategies according to the country and the medical discipline concerned. Funding The authors have no support or funding to report.

International audience; Background: Arterial pressure lability is common during the process of replacing syringes used for norepinephrine infusions in critically ill patients. It is unclear if there is an optimal approach to minimise arterial pressure instability during this procedures. We investigated whether 'double pumping' changeover (DPC) or automated changeover (AC) reduced blood pressure lability in critically ill adults compared with quick syringe changeover (QC).Methods: Patients requiring a norepinephrine infusion syringe change were randomised in a non-blinded trial undertaken in six ICUs. Randomisation was minimised by norepinephrine flow rate at inclusion and centre. The primary outcome was the frequency of increased/decreased mean arterial pressure (defined by 15 mm Hg from baseline measurements) within 15 min of switching the syringe compared with QC.Results: Patients (mean age: 64 (range:18-88)) yr were randomly assigned to QC (n=95), DPC (n=95), or AC (n=96). Increased MAP was the commonest consequence of syringe changeovers. MAP variability was most frequent after DPC (89/224 changeovers; 39.7%) compared with 57/223 (25.6%) changeovers after quick syringe switch and 46/181 (25.4%) in patients randomised to receive automated changeover (P=0.001). Fewer events occurred with QC compared with DPC (P=0.002). Sensitivity analysis based on mixed models showed that performing several changeovers on a single patient had no impact. Both type of changeover and norepinephrine dose before syringe changeover were independently associated with MAP variations >15 mm Hg.Conclusions: Quick changeover of norepinephrine syringes was associated with less blood pressure lability compared with DPC. The prevalence of MAP variations was the same between AC and QC.Clinical trial registration: NCT02304939.

Background Improving outcomes of older patients admitted into intensive care units (ICU) is a raising concern. This study aimed at determining which geriatric and ICU parameters were associated with in-hospital and long-term mortality in this population. Methods We conducted a prospective multicentric observational cohort study, including patients aged 75 years and older requiring mechanical ventilation, admitted between September 2012 and December 2013 into ICU of 13 French hospitals. Comprehensive geriatric assessment at ICU admission and ICU usual parameters were registered in a standardized manner. Survival was recorded and comprehensive geriatric assessment was updated after 1 year during a dedicated home visit. Results 501 patients were analyzed. 108 patients (21.6%) died during the hospital stay. One-year survival rate was 53.8% (IC 95% [49.2%; 58.2%]). Factors associated with increased in-hospital mortality were higher acute illness severity score, resuscitated cardiac arrest as primary ICU diagnosis, perception of anxiety and low quality of life by the proxy, and living in a chronic care facility before ICU admission. Among patients alive at hospital discharge, factors associated with increased 1-year mortality in multivariate analysis were longer duration of mechanical ventilation, all primary ICU diagnoses other than septic shock, a Katz-activities of daily living (ADL) score below 5 and living in a chronic care facility before ICU admission. Among the 163 survivors at 1 year who received a second comprehensive geriatric assessment, the ADL score (functional abilities) showed a significant but moderate decline over time, whereas the Mini-Zarit score (family burden) improved. No significant change in patients’ place of life was observed after 1 year, and quality of life was reported as happy-to-very-happy in 88% of survivors. Conclusions The mortality rate remains high among older ICU patients requiring mechanical ventilation. Factors associated with short- and long-term mortality combined geriatric and ICU criteria, which should be jointly evaluated in routine care. Clinical trial registration NCT01679171

International audience; PURPOSE: While patient’s reported autonomy (PRA) may help the physician to adapt the day of discharge, the link between postoperative ileus and length of stay and PRA is not known. The aim of this study was to evaluate the evolution of the PRA score during the postoperative period and to determine the factors possibly influencing such an evolution. METHODS: This retrospective study on a prospective database took place in a single centre over 14 months. PRA was defined by the by using part I of the Groningen Activity Restriction Scale known as activity of daily life [from 9 (best) to 45 (worst)]. RESULTS: Among the 101 patients operated on for elective or emergent colorectal surgery, 80% of the patients had recovered their preoperative PRA (±5 points) before discharge and maintained their PRA during the 2 days preceding discharge. While PRA was significantly decreased by surgery (P2 increased PRA (P=0.03). Age, emergency surgery and the occurrence of postoperative morbidity did not affect postoperative autonomy. Finally, enhanced recovery programs (ERP) tended to improve postoperative autonomy recovery (P=0.09). CONCLUSION: PRA may be used as a means of optimising a patient’s day of discharge following colorectal surgery.

The association between elevated plasma vitamin B12 (B12) level and solid cancers has been documented by two national registries. However, their design did not allow for the adjustment for other conditions associated with elevated B12. The objectives of this study were to confirm this association after the adjustment for all causes of elevated B12, and to study the variations according to the increasing B12 level, the type of cancers, and the presence of metastases. We compared 785 patients with B12 &ge, 1000 ng/L with 785 controls matched for sex and age with B12 &lt, 1000 ng/L. Analyses were adjusted for the causes of elevated B12: myeloid blood malignancies, acute or chronic liver diseases, chronic kidney failure, autoimmune or inflammatory diseases, and excessive B12 supplementation. A B12 &ge, 1000 ng/L was associated with the presence of solid cancer without metastases (OR 1.96 [95%CI: 1.18 to 3.25]) and with metastases (OR 4.21 [95%CI: 2.67 to 6.64]) after adjustment for all elevated B12-related causes. The strength of the association rose with the increasing B12 level, in particular in cases of metastases. No association between liver cancers and elevated B12 level was found after adjustment for chronic liver diseases. In conclusion, unexplained elevated B12 levels should be examined as a possible marker of solid cancer.

Background No recommendation exists about the timing and setting for tracheal intubation and mechanical ventilation in septic shock. Patients and methods This prospective multicenter observational study was conducted in 30 ICUs in France and Spain. All consecutive patients presenting with septic shock were eligible. The use of tracheal intubation was described across the participating ICUs. A multivariate analysis was performed to identify parameters associated with early intubation (before H8 following vasopressor onset). Results Eight hundred and fifty-nine patients were enrolled. Two hundred and nine patients were intubated early (24%, range 4.5–47%), across the 18 centers with at least 20 patients included. The cumulative intubation rate during the ICU stay was 324/859 (38%, range 14–65%). In the multivariate analysis, seven parameters were significantly associated with early intubation and ranked as follows by decreasing weight: Glasgow score, center effect, use of accessory respiratory muscles, lactate level, vasopressor dose, pH and inability to clear tracheal secretions. Global R-square of the model was only 60% indicating that 40% of the variability of the intubation process was related to other parameters than those entered in this analysis. Conclusion Neurological, respiratory and hemodynamic parameters only partially explained the use of tracheal intubation in septic shock patients. Center effect was important. Finally, a vast part of the variability of intubation remained unexplained by patient characteristics. Trial registration Clinical trials NCT02780466, registered on May 23, 2016. https://clinicaltrials.gov/ct2/show/NCT02780466?term=intubatic&draw=2&rank=1.

The advantages of enhanced recovery programs (ERP) after colorectal surgery for morbidity and length of stay are well known. On a longer term, evidence is much more limited. The aim of this study is to determine the impact of ERP on survival after 3 years of follow-up, following colorectal cancer surgery.All the patients undergoing resection for colorectal cancer between the years 2010 and 2014 were included. Patients were classified according to their compliance with the ERP ( 70 or ≥ 70%).Among the 206 patients included during the period, 129 were male (62.6%). The 3-year overall survival rate was 70.4% (145 patients) and relapse-free survival was 59.2% (122 patients). The survival after 3 years was influenced by the initial metastatic status (p 0.0001), operative morbidity (p 0.001), and the presence of peritumoral emboli (p = 0.006). However, the compliance with the ERP ≥ 70% did not influence overall survival (p = 0.63), nor relapse-free survival (p = 0.93). The same observations were found among the "at-risk" population (synchronous metastasis and postoperative complication).The ERP does not seem to influence the 3-year relapse-free survival after colorectal resection for cancer.

International audience; PURPOSE: The quantification of mtDNA in cumulus granulosa cells (CGCs) surrounding an oocyte has been positively linked with morphological embryonic quality. In the present study, we evaluated the link between the amount of mtDNA in CGCs surrounding an oocyte and the chances for the corresponding embryo of implanting and leading to an ongoing pregnancy.METHODS: This is an observational study, performed on 84 oocyte-cumulus-complexes (OCCs) having led to the replacement of an embryo in the maternal uterus, retrieved from 71 patients undergoing IVF with intracytoplasmic sperm. The OCCs were classified in two groups, one including 26 OCCs having led to an implanted embryo and the other including 58 OCCs having led to a non-implanted embryo. The average mtDNA content of CGCs was assessed by using a quantitative real-time PCR technique.RESULTS: Significantly higher mtDNA copy numbers in CGCs were associated with implanted embryos than with non-implanted embryos (mean 215 [sd 375] and 59 [sd 72], respectively; p CONCLUSION: During in vitro fertilization (IVF) procedures, the probability of the implantation of the embryo appears to be closely correlated to the mtDNA copy numbers in the CGCs. Our results highlight the interest of mtDNA quantification in GCGs as a biomarker of the potential of embryo implantation.

Aim: Accidental inoculation of humans with veterinary vaccines can lead to early and late complications. The aim of our study is to describe these complications and their risk factors.Methods: Pros...

Aims Over the last decades, Health-related Quality of Life (HRQoL) end-points have become an important outcome of the randomised controlled trials (RCTs). HRQoL methodology in RCTs has improved following international consensus recommendations. However, no international recommendations exist concerning the statistical analysis of such data. The aim of our study was to identify and characterise the quality of the statistical methods commonly used for analysing HRQoL data in cancer RCTs. Methods Building on our recently published systematic review, we analysed a total of 33 published RCTs studying the HRQoL methods reported in RCTs since 1991. We focussed on the ability of the methods to deal with the three major problems commonly encountered when analysing HRQoL data: their multidimensional and longitudinal structure and the commonly high rate of missing data. Results All studies reported HRQoL being assessed repeatedly over time for a period ranging from 2 to 36 months. Missing data were common, with compliance rates ranging from 45% to 90%. From the 33 studies considered, 12 different statistical methods were identified. Twenty-nine studies analysed each of the questionnaire sub-dimensions without type I error adjustment. Thirteen studies repeated the HRQoL analysis at each assessment time again without type I error adjustment. Only 8 studies used methods suitable for repeated measurements. Conclusion Our findings show a lack of consistency in statistical methods for analysing HRQoL data. Problems related to multiple comparisons were rarely considered leading to a high risk of false positive results. It is therefore critical that international recommendations for improving such statistical practices are developed.

International audience; Background. Admission of allogeneic stem cell transplantation (SCT) recipients to the intensive care unit (ICU) remains controversial , especially when graft-versus-host disease (GVHD) is present. Methods. We performed a retrospective study to assess prognostic factors of survival in all allogeneic SCT recipients admitted to the ICU between 2002 and 2013 in our center which has flexible admission criteria, especially regarding GVHD. Results. Of 349 patients who underwent allogeneic SCT during the study period, 92 patients (26%) were admitted to the ICU. Intensive care unit and hospital discharge rates were 66% and 46%, respectively , whereas 1 year survival was 24%. Acute GVHD, either grade III to IV (30 patients, 33%) or refractory (12 patients, 13%) had a nonsignificant impact on hospital mortality (odds ratio [OR], 2.1; P = 0.1; OR, 5, P = 0.05, respectively). Fifty percent of patients required invasive mechanical ventilation, 30% required vasopressors, 17% required renal replacement therapy, and 28% had liver impairment (bilirubin >34 μmol/L), each of these parameters defining organ failure. Mortality was closely associated with the number of organ failures as hospital discharge rates were 69%, 50%, 42%, and 0% among patients with 0 (26 patients), 1 (26 patients), 2 (26 patients), and 3 to 4 (14 patients) organ failures, respectively (OR, 2.7; 95% confidence interval, 1.6-4.6; P < 0.001 according to the number of organ failures). Conclusions. Early mortality of allogeneic SCT recipients admitted to the ICU is especially influenced by the number of organ failures and therefore patients with 0 to 2 organ failures should be considered if required. Refractory GVHD affects survival but not within the confined ICU admission.

To assess both severe maternal and neonatal mortality and morbidity after attempted operative vaginal deliveries by residents under supervision and by attending obstetricians.Secondary analysis of a 5-year prospective study with cross-sectional analysis including 2192 women with live singleton term fetuses in vertex presentation who underwent an attempted operative vaginal delivery in a tertiary care university hospital. Obstetricians who attempted or performed an operative vaginal delivery were classified into 2 groups according to their level of experience: attending obstetricians (who had 5 years or more of experience) and obstetric residents (who had less than 5 years of experience) under the supervision of an attending obstetrician. We used multivariate logistic regression and propensity score methods to compare outcomes associated with attending obstetricians and obstetric residents. Severe maternal morbidity was defined as third- or fourth-degree perineal laceration, perineal hematoma, cervical laceration, extended uterine incision for cesareans, postpartum hemorrhage1500 mL, surgical hemostatic procedures, uterine artery embolization, blood transfusion, infection, thromboembolic events, admission to the intensive care unit, or maternal death; severe neonatal morbidity was defined as a 5-minute Apgar score7, umbilical artery pH7.00, need for resuscitation or intubation, neonatal trauma, intraventricular hemorrhage greater than grade 2, neonatal intensive care unit admission for more than 24 hours, convulsions, sepsis, or neonatal death.High prepregnancy body mass index, high dose of oxytocin, manual rotation, persistent occiput posterior or transverse positions, operating room delivery, midpelvic delivery, forceps, and spatulas were significantly more frequent in deliveries managed by attending obstetricians than residents whereas a second-stage pushing phase longer than 30 minutes was significantly more frequent in deliveries managed by residents. The rate of severe maternal morbidity was 7.8% (115/1475) for residents vs 9.9% (48/484) for attending obstetricians; for severe neonatal morbidity, the rates were 8.3% (123/1475) vs 15.1% (73/484), respectively. In the univariate, multivariable, and sensitivity analyses, attempted operative vaginal delivery managed by a resident was significantly and inversely associated with severe neonatal but not maternal morbidity. After propensity score matching, delivery managed by a resident was not significantly associated with severe maternal morbidity (adjusted odds ratio, 0.74; 95% confidence interval, 0.39-1.38) and was no longer associated with neonatal morbidity (adjusted odds ratio, 0.51; 95% confidence interval, 0.25-1.04).Management of attempted operative vaginal deliveries by residents under the supervision of attending obstetricians, compared with by the attending obstetricians themselves, does not appear to be associated with either maternal or neonatal morbidity. These reassuring results support the continued use of residency programs for training in operative vaginal deliveries under the supervision of attending obstetricians.

Objectives Pasteurella bacteraemia is rare, but has been associated with a high mortality rate. The aim of this study was to estimate the impact of comorbidities on patients with Pasteurella bacteraemia. Methods All cases of Pasteurella bacteraemia in adults treated in our centre between January 2008 and December 2017 were included retrospectively and compared with cases identified in a systematic review of the literature via MEDLINE covering the years 1951–2017. The epidemiological, bacteriological, and clinical data were collected, as well as the instances of death after 30 days. Results Twenty cases of Pasteurella bacteraemia identified in our centre and 99 cases from the literature review were included. A major comorbidity was found in 80/119 (67.2%) patients. The death rate at 30 days was 31.1%. The most common comorbidities were cirrhosis, immunosuppressive therapy, and malignant diseases. Age was not associated with mortality. On multivariate analysis, the only factor associated with mortality was a major comorbidity (odds ratio 2.78, 95% confidence interval 1.01–7.70; p = 0.04). Conclusions This study confirms the high mortality rate and highlights the importance of the host background, independent of age, in Pasteurella bacteraemia. Clinicians should be aware of the comorbidities in cases of Pasteurella infection, due to the poor prognosis of bacteraemia.

Introduction The prevalence of type 2 diabetes (T2D) continues to rise across the world. Metformin is still considered the "gold standard" and is, therefore, increasingly prescribed. Monitoring of metformin continues to be debated because of its association with lactic acidosis (MALA), a rare but life-threatening complication. The aim of this study was to identify the main individual characteristics associated with severe poisoning in self-poisonings and therapeutic accidents reported at the Western France Poison Control Centre (PCC). Methods Retrospective study of metformin poisoning from September 1999 to September 2016 at the Western France PCC recorded in the French PCC's database (SICAP). The end-point was clinically high severity (mortality and/or cardiovascular shock and/or GCS ≤ 7/15). Results Of the 382 cases included, 197 concerned acute accidental exposures, 127 self-poisonings and 58 therapeutic accidents. MALA concerned 63 patients: 44 therapeutic accidents and 19 self-poisonings. High severity concerned 59 patients: 47 therapeutic accidents and 12 self-poisonings. T2D and age > 60 significantly increase the risk of high severity (OR 7.7, CI [1.54-38.41]; P = 0.013; OR 3.5, CI [1.60-7.84]; P = 0.002, respectively). Conclusions Metformin may lead to MALA and severe poisoning in therapeutic accidents but also in self-poisoning circumstances. Among reported cases, T2D history and age >60 increase the risk of serious poisoning. Monitoring of their treatment should be taken seriously especially in the event of digestive symptoms such as diarrhoea.

International audience; BACKGROUND: Increased renal resistive index (RI) measured by Doppler ultrasonography has been shown to be associated with acute kidney injury (AKI) in septic patients. However, its clinical use is limited by poor sensitivity and specificity which may be explained by its numerous determinants [in particular mean arterial pressure (MAP)]. We measured, in patients with septic shock, RI at different MAP levels over a short period of time on the admission day to ICU (D1) and every 3days until day 10 (D10) to define the determinants of RI and study specifically the relationship between RI and MAP.RESULTS: Consecutive patients with septic shock without preexisting chronic renal dysfunction were included in this prospective cohort study in two ICUs. Sixty-five patients were included in the study. Thirty-three (50.8%) and 15 (23.1%) patients had a history of chronic hypertension or diabetes, respectively. At D3, 35 patients presented AKI with AKIN 2 or 3 criteria (severe AKI, AKIN2-3 group) and 30 presented no AKIN or AKIN 1 criteria (AKIN0-1 group). As previously described, RI at D1 was higher in the AKIN2-3 group than in the AKIN0-1 group (0.73 interquartile range [0.67; 0.78] vs. 0.67 [0.59; 0.72], p = 0.001). A linear mixed model for predicting RI from D1 to D10 showed that an increase in pulse pressure, presence of severe AKI and additional day of ICU hospitalization were associated with an increase in RI. An increase in MAP and recovery from severe AKI were associated with a decrease in RI. In the presence of chronic hypertension or diabetes, an increase in MAP resulted in a lower decrease in RI, than in the absence of such factors. Presence of AKI at D3 did not impact the relationship between MAP and RI.CONCLUSIONS: Severe AKI was associated with a reversible increase in RI without significant interaction with the relationship between MAP and RI. Conversely, the presence of chronic hypertension and/or diabetes interacted with this relationship.

STUDY QUESTIONDoes ageing affect the kinetics of the mitochondrial pool during oogenesis and early embryogenesis?SUMMARY ANSWERWhile we found no age-related change during oogenesis, the kinetics of mitochondrial DNA content and the expression of the factors involved in mitochondrial biogenesis appeared to be significantly altered during embryogenesis.WHAT IS KNOWN ALREADYOocyte mitochondria are necessary for embryonic development. The morphological and functional alterations of mitochondria, as well as the qualitative and quantitative mtDNA anomalies, observed during ovarian ageing may be responsible for the alteration of oocyte competence and embryonic development.STUDY DESIGN, SIZE, DURATIONThe study, conducted from November 2016 to November 2017, used 40 mice aged 5–8 weeks and 45 mice aged 9–11 months (C57Bl6/CBA F(1)). A total of 488 immature oocytes, with a diameter ranging from 20 μm to more than 80 μm, were collected from ovaries, and 1088 mature oocytes or embryos at different developmental stages (two PN, one-cell, i.e. syngamy, two-cell, four-cell, eight-cell, morula and blastocyst) were obtained after ovarian stimulation and, for embryos, mating.PARTICIPANTS/MATERIALS, SETTING, METHODSMitochondrial DNA was quantified by quantitative PCR. We used quantitative reverse transcriptase PCR (RT-PCR) (microfluidic method) to study the relative expression of three genes involved in the key steps of embryogenesis, i.e. embryonic genome activation (HSPA1) and differentiation (CDX2 and NANOG), two mtDNA genes (CYB and ND2) and five genes essential for mitochondrial biogenesis (PPARGC1A, NRF1, POLG, TFAM and PRKAA). The statistical analysis was based on mixed linear regression models applying a logistic link function (STATA v13.1 software), with values of P MAIN RESULTS AND THE ROLE OF CHANCEDuring oogenesis, there was a significant increase in oocyte mtDNA content (P LARGE SCALE DATAN/A.LIMITATIONS, REASONS FOR CAUTIONBecause of the ethical impossibility of working on a human, this study was conducted only on a murine model. As superovulation was used, we cannot totally exclude that the differences observed were, at least partially, influenced by differences in ovarian response between young and old mice.WIDER IMPLICATIONS OF THE FINDINGSOur findings suggest a pathophysiological explanation for the link observed between mitochondria and the deterioration of oocyte quality and early embryonic development with age.STUDY FUNDING/COMPETING INTEREST(S)This work was supported by the University of Angers, France, by the French national research centres INSERM and the CNRS and, in part, by PHASE Division, INRA. There are no competing interests.

While the suspension-feeding sea cucumber Cucumaria frondosa is commercially exploited in the North Atlantic and is considered to have potential for integrated aquaculture, the impact of environmental conditions on its behaviour and population structure remains incompletely understood. The present study showed that adults are not photosensitive; they do not exhibit any preference for either illuminated or shaded areas. Within each photoperiod treatment, analyses of the daily activity cycle revealed that the proportion of individuals with feeding tentacles deployed did not change over time; however, the proportion of moving individuals increased in the dark phase under the 12 h light/12 dark regime, but remained constant under continuous light or darkness. Hence, from an aquaculture perspective, long days (i.e. summer photoperiod) might decrease the time spent moving in favour of feeding, potentially shifting the energy budget toward faster growth. Variations in phytoplankton concentration modulated the deployment of tentacles but did not trigger any displacement toward the food source, indicating that feeding responds directly to the presence of food. Moreover, C. frondosa exhibited a clear preference for substrates composed of bare rocks and rocks with coralline algae and displayed a weak preference for darker substrate backgrounds. Together, these findings highlight how some key environmental factors can govern the feeding, locomotor activities, and eventual distribution of cold-water suspension-feeding sea cucumbers.

Postoperative ileus (POI) occurrence within enhanced recovery programs (ERPs) has decreased. Also, intra-abdominal complications (IAC) such as anastomotic leakage (AL) generally present late. The aim was to characterize the link between POI and the other complications occurring after surgery.This retrospective analysis of a prospective database was conducted by the Francophone Group for Enhanced Recovery after Surgery. POI was considered to be present if gastrointestinal functions had not been recovered within 3 days following surgery or if a nasogastric tube replacement was required.Of the 2773 patients who took part in the study, 2335 underwent colorectal resections (83.8%) for cancer, benign tumors, inflammatory bowel disease, and diverticulosis. Among the 2335 patients, 309 (13.2%) experienced POI, including 185 (59.9%) cases of secondary POI. Adjusted for well-known risk factors (male gender, need for stoma, right hemicolectomy, surgery duration, laparotomy, and conversion to open surgery), POI was associated with abdominal complications (OR = 4.55; 95% confidence interval (CI): 3.30-6.28), urinary retention (OR = 1.75; 95% CI: 1.05-2.92), pulmonary complications (OR = 4.55; 95% CI: 2.04-9.97), and cardiological complications (OR = 3.01; 95% CI: 1.15-8.02). Among the abdominal complications, AL and IAC were most strongly associated with POI (respectively, OR = 5.97; 95% CI: 3.74-8.88 and OR = 5.76; 95% CI: 3.56-10.62).Within ERPs, POI should not be considered as usual. There is a significant link between POI and IAC. Since POI is an early-onset clinical sign, its occurrence should alert the physician and prompt them to consider performing CT scans in order to investigate other potential morbidities.

International audience; BACKGROUND: Although continuous renal replacement therapy (CRRT) is common, unplanned interruptions (UI) often limit its usefulness. In many units, nurses are responsible for CRRT management. We hypothesized that a nurse training program based on high-fidelity simulation would reduce the rate of interrupted sessions.METHODS: We performed a 2-phase (training and evaluation), randomized, single-center, open study: During the training phase, intensive care unit nurses underwent a 6-hour training program and were randomized to receive (intervention) or not (control) an additional high-fidelity simulation training (6 hours). During the evaluation phase, management of CRRT sessions was randomized to either intervention or control nurses. Sessions were defined as UI if they were interrupted and the interruption was not prescribed in writing more than 3 hours before.RESULTS: Study nurses had experience with hemodialysis, but no experience with CRRT before training. Intervention nurses had higher scores than control nurses on the knowledge tests (grade, median [Q1-Q3], 14 [10.5-15] vs 11 [10-12]/20; P = .044). During a 13-month period, 106 sessions were randomized (n = 53/group) among 50 patients (mean age 70 ± 13 years, mean simplified acute physiology II score 69 [54-96]). Twenty-one sessions were not analyzed (4 were not performed and 17 patients died during sessions). Among the 42 intervention and 43 control sessions analyzed, 25 (59%) and 38 (88%) were labeled as UI (relative risk [95% CI], 0.67 [0.51-0.88]; P = .002). Intervention nurses required help significantly less frequently (0 [0-1] vs 3 [1-4] times/session; P < .0001). The 2 factors associated with UI in multilevel mixed-effects logistic regression were Sequential Organ Failure Assessment score (odds ratio [95% CI], 0.81 [0.65-99]; P = .047) and the intervention group (odds ratio, 0.19 [0.05-0.73]; P = .015).CONCLUSIONS: High-fidelity simulation nurse training reduced the rate of UI of CRRT sessions and the need for nurses to request assistance. This intervention may be particularly useful in the context of frequent nursing staff turnover.

Primary central nervous system lymphomas (PCNSL) are non-Hodgkin lymphomas strictly localized to the CNS, occurring mainly in elderly patients with comorbidities. Current treatment in fit patients relies on high-dose methotrexate and high-dose cytarabine. The aim of this study was to evaluate the efficacy and feasibility of this treatment in elderly patients and to assess potential prognostic factors associated with survival. We conducted a retrospective study in two centers between January 2008 and September 2015 including 35 elderly immunocompetent patients who received first-line treatment with high-dose methotrexate. With a median follow-up of 19.8 months (range: 1.7–73.4 months), median overall survival (OS) was 39.5 months (95% confidence interval (95% CI): 18.3–60.7) and median progression-free survival (PFS) was 25.8 months (95% CI: 5.2–46.4). In univariate analysis, administration of high-dose cytarabine and achieving a relative dose intensity for methotrexate > 75% were associated with increased OS (p = 0.006 and p = 0.003, respectively) and PFS (p = 0.003 and p = 0.04, respectively) whereas comorbidities, defined by a CIRS-G score ≥ 8, were associated with decreased OS and PFS (p = 0.02 and p = 0.04, respectively). A high MSKCC score was associated with decreased OS (p = 0.02). In multivariate analysis, administration of high-dose cytarabine was associated with increased OS and PFS (p = 0.02 and p = 0.007, respectively). Comorbidities and relative dose intensity for methotrexate are important for the prognosis of elderly patients with PCNSL. These results must be confirmed in prospective trials.

Background Endothelial dysfunction, a pathophysiologic determinant of atherogenesis, has been found to occur in obstructive sleep apnea syndrome (OSA) and is improved by continuous positive airway pressure (CPAP). However, the efficacy of CPAP therapy is limited by variable adherence. Alternative treatment strategies are needed. The impact of polyphenols on endothelial function has never been evaluated in OSA. Objective We evaluated the impact of 1-mo supplementation with grape juice polyphenols (GJPs) on the reactive hyperemia index (RHI), a validated measure of endothelial function in patients with severe OSA. Methods Forty participants [75% men, median (IQR) age: 61 y (34, 64 y), BMI (in kg/m2): 30.6 (20.9, 33.7)] with severe OSA [median apnea-hypopnea index 43/h (33/h, 56/h)] were randomly assigned to receive GJPs (300 mg/d; n = 20) or placebo (n = 20) for 1 mo. The primary outcome was the change in RHI between baseline and after 1 mo of GJPs or placebo. Secondary outcome measures included changes in blood pressure (BP), heart rate (HR), and polysomnographic indexes. Results No significant differences in RHI and BP outcomes were observed between the GJPs and placebo groups. A significant between-group difference was observed for HR changes [-1 bpm (-5, +5 bpm) in the GJPs group compared with +6 bpm (+3, +10 bpm) in the placebo group; P = 0.001]. A significant decrease in total sleep time was observed in the GJPs group compared with the placebo group [-10 min (-33, 6 min) compared with +15 min (-12, 40 min), respectively; P = 0.02], with no between-group differences in the distribution of sleep stages. Conclusions In participants with severe OSA and no overt cardiovascular disease, 1-mo GJP supplementation had no effect on endothelial function. This trial was registered at clinicaltrials.gov as NCT01977924.

Whole-body chimaeras (organisms composed of genetically distinct cells) have been directly observed in modular/colonial organisms (e.g. corals, sponges, ascidians); whereas in unitary deuterostosmes (including mammals) they have only been detected indirectly through molecular analysis. Here, we document for the first time the step-by-step development of whole-body chimaeras in the holothuroid Cucumaria frondosa , a unitary deuterostome belonging to the phylum Echinodermata. To the best of our knowledge, this is the most derived unitary metazoan in which direct investigation of zygote fusibility has been undertaken. Fusion occurred among hatched blastulae, never during earlier (unhatched) or later (larval) stages. The fully fused chimaeric propagules were two to five times larger than non-chimaeric embryos. Fusion was positively correlated with propagule density and facilitated by the natural tendency of early embryos to agglomerate. The discovery of natural chimaerism in a unitary deuterostome that possesses large externally fertilized eggs provides a framework to explore key aspects of evolutionary biology, histocompatibility and cell transplantation in biomedical research.

International audience; Background and aimsThe first cause of low-dose acetylsalicylic-acid (ASA) inefficacy is poor adherence to treatment. No non-invasive technique is available to assess ASA intake. Current-induced vasodilation (CIV) was found abolished in healthy volunteers after low-dose ASA intake. We tested clinical characteristics, treatments, and comorbid conditions influencing CIV amplitude in vascular patients.MethodsCIV was tested in 400 patients (277 males and 123 females, aged 65.4 ± 13.4 years). We focused on clinical characteristics, treatments, and comorbid conditions as covariates of CIV amplitude. We studied the CIV amplitude to covariate relationships with multivariate linear regression and receiver operating characteristics (ROC).ResultsThe multivariate linear model determined that ASA intake within the last 48 h and the interaction between ASA intake and body mass index (BMI) were the sole covariates associated with CIV amplitude. For the whole population, the area under the ROC curve (AUC) for CIV to predict ASA intake was 0.853 [95% confidence interval (CI): 0.814–0.892]. Considering separately the areas observed for non-obese (BMI ≤30, n = 303) and obese (BMI>30, n = 93) patients, the AUC [95% CI] was 0.873 [0.832–0.915] and 0.776 [0.675–0.878], respectively (p = 0.083).ConclusionsASA is the only drug that affects the amplitude of CIV response observed after galvanic current application to the skin of vascular patients. CIV depends on BMI but not age or gender. As such, CIV appears to be a potential objective marker of ASA intake and could facilitate future non-invasive assessments of adherence to ASA treatment.

International audience; The benefit of early admission of allogeneic stem cell transplantation (SCT) recipients to the intensive care unit (ICU) as soon as they develop organ injury is unknown. We performed a retrospective study on 92 patients admitted to the ICU to determine the impact of time from organ injury to ICU admission on outcome. The number of organ injuries prior to ICU admission was associated with an increased in-hospital mortality (OR 1.7, 95% CI 1–2.7, p = 0.04). Time between first organ injury and ICU admission was also associated with an increased in-hospital survival (OR 1.4, 95% CI 1.1–1.8, p = 0.02). A score combining these two covariates—the number of organ injuries/day (sum of days spent with each individual organ injury)—further improved the prediction of hospital survival. Patients with more organ injuries/day had significantly higher in-hospital mortality rate even after adjustment for refractory acute GVHD and the SOFA (OR 1.3, 95% CI 1–1.7, p = 0.02). Early ICU admission of allogeneic SCT recipients to the ICU as soon as they develop organ injury is associated with decreased in-hospital mortality.

IntroductionAs patient assessment of health-related quality of life (HRQOL) in cancer clinical trials has increased over the years, so has the need to attach meaningful interpretations to differences in HRQOL scores between groups and changes within groups. Determining what represents a minimally important difference (MID) in HRQOL scores is useful to clinicians, patients and researchers, and can be used as a benchmark for assessing the success of a healthcare intervention. Our objective is to provide an evidence-based protocol to determine MIDs for the European Organisation for Research and Treatment for Cancer Quality of life Questionnaire core 30 (EORTC QLQ-C30). We will mainly focus on MID estimation for group-level comparisons. Responder thresholds for individual-level change will also be estimated.Methods and analysisData will be derived from published phase II and III EORTC trials that used the QLQ-C30 instrument, covering several cancer sites. We will use individual patient data to estimate MIDs for different cancer sites separately. Focus is on anchor-based methods. Anchors will be selected per disease site from available data. A disease-oriented and methodological panel will provide independent guidance on anchor selection. We aim to construct multiple clinical anchors per QLQ-C30 scale and also to compare with several anchor-based methods. The effects of covariates, for example, gender, age, disease stage and so on, will also be investigated. We will examine how our estimated MIDs compare with previously published guidelines, hence further contributing to robust MID guidelines for the EORTC QLQ-C30.Ethics and disseminationAll patient data originate from completed clinical trials with mandatory written informed consent, approved by local ethical committees. Our findings will be presented at scientific conferences, disseminated via peer-reviewed publications and also compiled in a MID ‘blue book’ which will be made available online on the EORTC Quality of Life Group website as a free guideline document.

Cardiac rehabilitation (CR) combines therapeutic education with physical training and is recognized to reduce mortality rates by approximately 22% following myocardial infarction (MI) [(1)][1]. Despite its broad acceptance, some studies have reported that CR may be harmful, in terms of left

OBJECTIVE Splanchnic vein thrombosis (SVT) is a potentially severe complication of pancreatitis. The aim of this single-center, retrospective cohort study was to investigate the incidence of SVT and to determine the connected risk factors. METHODS All consecutive patients with acute pancreatitis (AP) managed in our hospital were included. The primary outcome was the occurrence of SVT and data was collected in accordance with Ranson's criteria. RESULTS A total of 318 patients were included, of whom 124 (39.0%) were women. Biliary lithiasis was the main cause of pancreatitis (n = 156, 49.1%). A total of 19 (6.0%) SVT were identified. In univariate analysis, alcohol intake, smoking and male gender were associated with SVT (P = 0.005, 0.003 and 0.007, respectively). Biological parameters significantly associated with thrombosis were lactate dehydrogenase (LDH) 75% was a protective factor against thrombosis (OR 0.148, P = 0.019). Leukocytes >10 × 10(9)/L (OR 6.397, P = 0.034), hyperglycemia (≥ 10 mmol/L) (OR 6.845, P = 0.023), LDH

Apart from sharing common ancestry with chordates, sea cucumbers exhibit a unique morphology and exceptional regenerative capacity. Here we present the complete genome sequence of an economically important sea cucumber, A. japonicus, generated using Illumina and PacBio platforms, to achieve an assembly of approximately 805 Mb (contig N50 of 190 Kb and scaffold N50 of 486 Kb), with 30,350 protein-coding genes and high continuity. We used this resource to explore key genetic mechanisms behind the unique biological characters of sea cucumbers. Phylogenetic and comparative genomic analyses revealed the presence of marker genes associated with notochord and gill slits, suggesting that these chordate features were present in ancestral echinoderms. The unique shape and weak mineralization of the sea cucumber adult body were also preliminarily explained by the contraction of biomineralization genes. Genome, transcriptome, and proteome analyses of organ regrowth after induced evisceration provided insight into the molecular underpinnings of visceral regeneration, including a specific tandem-duplicated prostatic secretory protein of 94 amino acids (PSP94)-like gene family and a significantly expanded fibrinogen-related protein (FREP) gene family. This high-quality genome resource will provide a useful framework for future research into biological processes and evolution in deuterostomes, including remarkable regenerative abilities that could have medical applications. Moreover, the multiomics data will be of prime value for commercial sea cucumber breeding programs., Author summary Echinoderms, ubiquitous in the marine environment, are important from evolutionary, ecological, and socioeconomic perspectives. Together with chordates and hemichordates, they form the deuterostome clade, making them a crucial node in the study of chordate ancestry. Within echinoderms, class Holothuroidea is unique; its members (the sea cucumbers) display remarkable regenerative abilities and play key roles as sediment bioturbators and symbiotic hosts, and many are prized in the seafood and pharmaceutical industries. The sea cucumber genome therefore has the potential to significantly contribute to our understanding of important evolutionary and biological processes and help enhance aquaculture programs. Here we present a high-quality genome sequence for the economically important species Apostichopus japonicus. Through comparative analyses, we identified 763 echinoderm-specific gene families enriched in genes encoding membrane proteins, ion channels, and signal transduction proteins. Marker genes associated with the notochord and gill slits were also found, providing valuable insight into the origin of chordates. The reduced number and low expression levels of biomineralization genes reflect the skeletal degeneration seen in sea cucumbers. Importantly, 2 gene families appeared to be expanded in A. japonicus and may play crucial roles in its heightened regenerative potential. Together, findings from the sea cucumber genome provide important and novel insights into echinoderm and deuterostome biology.

Summary Background Some patients who are at high surgical risk because of multiple co-morbidities undergo balloon aortic valvuloplasty (BAV) as a bridge therapy towards transcatheter aortic-valve implantation (TAVI). Aim The aim of this study was to compare the clinical course of patients with or without previous BAV who underwent TAVI and were included in the FRANCE 2 registry. Methods From January 2010 to December 2011, 3953 patients underwent TAVI. Survival analysis was done by multivariable regression and propensity-score analysis to adjust for confounders. Results Patients in the previous BAV group ( n = 664, 16.8%) were older than patients in the primary TAVI group. The logistic EuroSCORE I and the rates of co-morbidities and symptoms were higher in the previous BAV group. Procedural success was similar in both groups, as was postprocedural aortic regurgitation grade ≥ 2/4. The 1-month mortality rates from all causes were 12.5 and 8.7%, respectively, in the previous BAV and primary TAVI groups ( P = 0.001). The 1-month to 1-year mortality rates were similar in both groups. Previous BAV was not an independent predictor of 1-month mortality (hazard ratio 1.44, 95% confidence interval 0.90–2.34; P = 0.14) or 1-month to 1-year mortality. Conclusions Crude 1-month mortality was higher in patients with previous BAV. Nevertheless, precarious preoperative status, but not previous BAV, was associated with mortality, and is the only marker that should be considered as detrimental at the time of preTAVI reassessment.

Objective To evaluate the effect of the fetal head station at attempted operative vaginal delivery (aOVD), and specifically midpelvic or low aOVD, on female and male sexual function and symptoms of postpartum depression (PPD) at 6 months. Design Prospective population-based cohort study. Setting 1,941 women with singleton term fetuses in vertex presentation with midpelvic or low aOVD between 2008 and 2013 in a tertiary care university hospital. Methods Symptoms of female sexual dysfunction using the Pelvic Organ Prolapse/Urinary Incontinence/Sexual Function Short Form Questionnaire (PISQ-12), symptoms of PPD using the Edinburgh Postnatal Depression Scale (EPDS) score, symptoms of male sexual dysfunction using the International Index of Erectile Function (IIEF-15) and perineal pain were assessed 6 months after aOVD. We measured the association between midpelvic or low aOVD and symptoms of female and male sexual function and symptoms of PPD at 6 months using multiple regression and adjusting for demographics, and risk factors of sexual dysfunction, symptoms of PPD and perineal pain with adjusted odds ratios (aORs) and 95% confidence intervals (95% CI). Results The study included 907 women (46.7%) who responded to the questionnaire; 18.4% (167/907) had midpelvic aOVD, and 81.6% (740/907) low. Most women (873/907 [96.3%]) of those with partners reported sexual activity at 6 months. No significant difference was observed for PISQ-12, EPDS, IIEF-15 scores and perineal pain between mid and low pelvic groups. Compared with low pelvic aOVD, midpelvic aOVD was not significantly associated with either female or male sexual dysfunction (p = 0.89 and p = 0.76, respectively), or maternal symptoms of PPD (p = 0.83). Perineal pain significantly increased the risk of male and female sexual dysfunction and maternal symptoms of PPD at 6 months (p = 0.02, p = 0.006, and p = 0.02, respectively). Conclusion Midpelvic compared with low pelvic aOVD was not associated with an increase in sexual dysfunction, nor with symptoms of PPD at 6 months.

Accumulating evidence highlights natural killer (NK) cell parameters as potential prognostic factors in cancer patients, which provides a strong rationale for developing therapeutic strategies aiming at restoring NK cell. However, reaching this point warrants better characterization of tumor-induced NK cell alterations. Our group recently reported heterogeneous NK maturation in acute myeloid leukemia (AML) patients. However, the clinical significance of such observations remained to be assessed on a larger cohort of patients. NK maturation based on expression of CD56, CD57, and KIR was assessed by flow cytometry in newly diagnosed AML patients (N = 87 patients from GOELAMS-LAM-IR-2006 multicenter trial). Clinical outcome was evaluated with regard to NK maturation profiles. Unsupervised integrated analysis of NK maturation markers confirmed the existence of three distinct groups of patients [hypomaturation (24.1%), intermediate maturation (66.7%), and hypermaturation (9.2%)]. In univariate analysis, significant differences in overall survival (OS) (P = 0.0006) and relapse-free survival (RFS) (P

International audience; NKp46 is a major determinant of natural killer (NK) cell function and it is implicated in tumor immune surveillance in acute myeloid leukemia (AML). The purpose of this study was to investigate the prognostic significance of NKp46 expression in an independent cohort of patients with AML, and to investigate the impact of NKp46 on clinical outcome after allogeneic stem cell transplantation (allo-SCT).NKp46 expression was assessed at diagnosis on NK cells by flow cytometry (N = 180 patients). Clinical outcome was evaluated with regard to NKp46 expression. Patients with NKp46high phenotype at diagnosis had better progression-free survival (PFS) and overall survival (OS) than patients with NKp46low phenotype (74.3% vs. 46.6%, p = 0.014; 82.6% vs. 57.1%, p = 0.010, respectively). In multivariate analysis, high NKp46 was an independent factor for improved OS (HR = 0.409, p = 0.010) and PFS (HR = 0.335, p = 0.011). Subgroup analysis revealed that allo-SCT had a favorable impact on PFS in patients with NKp46high phenotype (p = 0.025). By contrast, allo-SCT did not impact PFS in patients with low NKp46 expression (p = 0.303).In conclusion, we validate the prognostic value of NKp46 expression at diagnosis in AML. However, the prognostic value of NKp46 expression is limited to patients treated with allo-SCT, thus suggesting that NKp46 status may be predictive for allo-SCT responsiveness.

Subjective health measurements using Patient Reported Outcomes (PRO) are increasingly used in randomized trials, particularly for patient groups comparisons. Two main types of analytical strategies can be used for such data: Classical Test Theory (CTT) and Item Response Theory models (IRT). These two strategies display very similar characteristics when data are complete, but in the common case when data are missing, whether IRT or CTT would be the most appropriate remains unknown and was investigated using simulations. We simulated PRO data such as quality of life data. Missing responses to items were simulated as being completely random, depending on an observable covariate or on an unobserved latent trait. The considered CTT-based methods allowed comparing scores using complete-case analysis, personal mean imputations or multiple-imputations based on a two-way procedure. The IRT-based method was the Wald test on a Rasch model including a group covariate. The IRT-based method and the multiple-imputations-based method for CTT displayed the highest observed power and were the only unbiased method whatever the kind of missing data. Online software and Stata® modules compatibles with the innate mi impute suite are provided for performing such analyses. Traditional procedures (listwise deletion and personal mean imputations) should be avoided, due to inevitable problems of biases and lack of power.

International audience; BACKGROUND: Incarcerated hernias represent about 5-15% of all operated hernias. Tension-free mesh is the preferred technique for elective surgery due to low recurrence rates. There is however currently no consensus on the use of mesh for the treatment of incarcerated hernias, especially in case of bowel resection.AIM: The aims of this study were (i) to report our current practice for the treatment of incarcerated hernias, (ii) to identify risk factors for postoperative complications, and (iii) to assess the safety of mesh placement in potentially infected surgical fields.METHODS: This retrospective study included 166 consecutive patients who underwent emergency surgery for incarcerated hernia between January 2007 and January 2012 in two university hospitals. Demographics, surgical details, and short-term outcome were collected. Univariate analysis was employed to identify risk factors for overall, infectious, and major complications.RESULTS: Eighty-four patients (50.6%) presented inguinal hernias, 43 femoral (25.9%), 37 umbilical hernias (22.3%), and 2 mixed hernias (1.2%), respectively. Mesh was placed in 64 patients (38.5%), including 5 patients with concomitant bowel resection. Overall morbidity occurred in 56 patients (32.7%), and 8 patients (4.8%) developed surgical site infections (SSI). Univariate risk factors for overall complications were ASA grade 3/4 (P = 0.03), diabetes (P = 0.05), cardiopathy (P = 0.001), aspirin use (P = 0.023), and bowel resection (P = 0.001) which was also the only identified risk factor for SSI (P = 0.03). In multivariate analysis, only bowel incarceration was associated with a higher rate of major morbidity (OR = 14.04; P = 0.01).CONCLUSION: Morbidity after surgery for incarcerated hernia remains high and depends on comorbidities and surgical presentation. The use of mesh could become current practice even in case of bowel resection.

Objective To evaluate the effect of the fetal head station at attempted operative vaginal delivery (aOVD), and specifically midpelvic or low aOVD, on urinary incontinence (UI), anal incontinence (AI), and perineal pain at 6 months. Design Prospective cohort study. Setting 1941 women with singleton term fetuses in vertex presentation with midpelvic or low aOVD between 2008 and 2013 in a tertiary care university hospital. Methods Symptoms of urinary incontinence (UI) using the Bristol Female Lower Urinary Tract Symptoms questionnaire, and symptoms of anal incontinence (AI) severity using Fecal Incontinence Severity Index (FISI) were assessed 6 months after aOVD. We measured the association between midpelvic or low aOVD and symptoms of UI, AI, and perineal pain at 6 months using multiple regression and adjusting for demographics, and risk factors of UI and AI, with adjusted odds ratios (aORs) and 95% confidence intervals (95% CI). Results The study included 907 women (46.7%) who responded to the questionnaire; 18.4% (167/907) had midpelvic aOVD, and 81.6% (740/907) low; and none of women with symptoms of UI (26.6%, and 22.4%, respectively; p = 0.31), AI (15.9%, and 21.8%; p = 0.09), the FISI score, and perineal pain (17.2%, and 12.7%; p = 0.14) differed significantly between groups. The same was true for stress, urge, and mixed-type UI, severe UI and difficulty voiding. Compared with low pelvic aOVD, the aORs for symptoms of UI in midpelvic aOVD were 0.70 (0.46–1.05) and AI 1.42 (0.85–2.39). Third- and fourth-degree tears were a major risk factor of symptoms of UI (aOR 3.08, 95% CI 1.35–7.00) and AI (aOR 3.47, 95% CI 1.43–8.39). Conclusion Neither symptoms of urinary nor anal incontinence differed at 6 months among women who had midpelvic and low pelvic aOVD. These findings are reassuring and need further studies at long-term to confirm these short-term data.