Evaluation of preventive tract embolization with standardized gelatin sponge slurry on chest tube placement rate after CT-guided lung biopsy: a propensity score analysis.

BACKGROUND: To evaluate the effect of tract embolization (TE) with gelatin sponge slurries during a percutaneous lung biopsy on chest tube placement and to evaluate the predictive factors of chest tube placement. METHODS: Percutaneous CT-guided lung biopsies performed with (TE) or without (non-TE) tract embolization or between June 2012 and December 2021 at three referral tertiary centers were retrospectively analyzed. The exclusion criteria were mediastinal biopsies, pleural tumors, and tumors adjacent to the pleura without pleural crossing. Variables related to patients, tumors, and procedures were collected. Univariable and multivariable analyses were performed to determine risk factors for chest tube placement. Furthermore, the propensity score matching analysis was adopted to yield a matched cohort. RESULTS: A total of 1157 procedures in 1157 patients were analyzed, among which 560 (48.4%) were with TE (mean age 66.5 ± 9.2, 584 men). The rates of pneumothorax (44.9% vs. 26.1%, respectively; p < 0.001) and chest tube placement (4.8% vs. 2.3%, respectively; p < 0.001) were significantly higher in the non-TE group than in the TE group. No non-targeted embolization or systemic air embolism occurred. In the whole population, two protective factors for chest tube placement were found in univariate analysis: TE (OR 0.465 [0.239-0.904], p < 0.05) and prone position (OR 0.212 [0.094-0.482], p < 0.001). These data were confirmed in multivariate analysis (p < 0.001 and p < 0.0001 respectively). In the propensity matched cohort, TE reduces significatively the risk of chest tube insertion (OR = 0.44 [0.21-0.87], p < 0.05). CONCLUSIONS: The TE technique using standardized gelatin sponge slurry reduces the need for chest tube placement after percutaneous CT-guided lung biopsy. CRITICAL RELEVANCE STATEMENT: The tract embolization technique using standardized gelatin sponge slurry reduces the need for chest tube placement after percutaneous CT-guided lung biopsy. KEY POINTS: 1. Use of tract embolization with gelatine sponge slurry during percutaneous lung biopsy is safe. 2. Use of tract embolization significantly reduces the risk of chest tube insertion. 3. This is the first multicenter study to show the protective effect of tract embolization on chest tube insertion.

Rationale and design of the ULYSS trial: A randomized multicenter evaluation of the efficacy of early Impella CP implantation in acute coronary syndrome complicated by cardiogenic shock.

CONTEXT: Despite 20 years of improvement in acute coronary syndromes care, patients with acute myocardial infarction complicated by cardiogenic shock (AMICS) remains a major clinical challenge with a stable incidence and mortality. While intra-aortic balloon pump (IABP) did not meet its expectations, percutaneous mechanical circulatory supports (pMCS) with higher hemodynamic support, large availability and quick implementation may improve AMICS prognosis by enabling early hemodynamic stabilization and unloading. Both interventional and observational studies suggested a clinical benefit in selected patients of the IMPELLAⓇ CP device within in a well-defined therapeutic strategy. While promising, these preliminary results are challenged by others suggesting a higher rate of complications and possible poorer outcome. Given these conflicting data and its high cost, a randomized clinical trial is warranted to delineate the benefits and risks of this new therapeutic strategy. DESIGN: The ULYSS trial is a prospective randomized open label, 2 parallel multicenter clinical trial that plans to enroll patients with AMICS for whom an emergent percutaneous coronary intervention (PCI) is intended. Patients will be randomized to an experimental therapeutic strategy with pre-PCI implantation of an IMPELLAⓇ CP device on top of standard medical therapy or to a control group undergoing PCI and standard medical therapy. The primary objective of this study is to compare the efficacy of this experimental strategy by a composite end point of death, need to escalate to ECMO, long-term left ventricular assist device or heart transplantation at 1 month. Among secondary objectives 1-year efficacy, safety and cost effectiveness will be assessed. CLINICAL TRIAL REGISTRATION: NCT05366452.

Impact of targeted pulmonary arterial hypertension therapies in severe pulmonary hypertension in chronic lung diseases.

Research questions: Patients with severe pulmonary hypertension associated with chronic lung disease have a poor prognosis. Targeted pulmonary arterial hypertension therapies might improve exercise capacity and outcome, but there are no guidelines on treatments which are not recommended because of an unproven benefit, with discordant results from few studies in this context. The aim of our study was to evaluate targeted pulmonary arterial hypertension therapies for severe group 3 pulmonary hypertension patients. Study design and methods: We conducted an observational retrospective monocentre study on patients with severe group 3 pulmonary hypertension diagnosed on right heart catheterisation treated with targeted therapies. Primary outcome was an improvement of the distance on 6-min walk test of ≥30 m. Secondary end-points included changes in haemodynamics (pulmonary vascular resistance (PVR) and mean pulmonary arterial pressure (mPAP)) and identification of potential predictive factors of therapeutic response. Results: 139 patients were enrolled. Most patients had monotherapy with phosphodiesterase 5 inhibitors (n=128; 92%). Mean change in 6-min walk distance was +1.5 m after treatment (p=0.59). Forced expiratory volume in 1 s and forced vital capacity were not predictive factors for response. We found a significant improvement of PVR and mPAP of -1.0 Wood Units (p<0.001) and -4 mmHg (p<0.001), respectively, under treatment. 18% of patients had to withdraw treatment for intolerance. Treatment duration <3 months was associated with poor survival (hazard ratio 2.75, p=0.0005). Conclusion: Oral targeted pulmonary arterial hypertension therapies do not improve exercise capacity in patients with severe pulmonary hypertension associated with chronic lung disease, but could improve haemodynamic parameters.

Is the Epithor conversion score reliable in robotic-assisted surgery anatomical lung resection?

OBJECTIVES: Despite an improvement in surgical abilities, the need for an intraoperative switch from a minimally invasive procedure towards an open surgery (conversion) still remains. To anticipate this risk, the Epithor conversion score (ECS) has been described for video-assisted thoracoscopic surgery (VATS). Our objective was to determine if this score, developed for VATS, is applicable in robotic-assisted thoracoscopic surgery (RATS). METHODS: This was a retrospective monocentric study from January 2006 to June 2022, and data were obtained from the EPITHOR database. Patients included were those who underwent anatomic lung resection either by VATS or RATS. The ECS was calculated for all patients studied. Discrimination and calibration of the test were measured by the area under the curve and Hosmer-Lemeshow test. RESULTS: A total of 1685 were included. There were 183/1299 conversions in the VATS group (14.1%) and 27/386 conversions in the RATS group (6.9%). Patients in the RATS group had fewer antiplatelet therapy and peripheral arterial disease. There were more segmentectomies in the VATS group. As for test discrimination, the area under the curve was 0.66 [0.56-0.78] in the RATS group and 0.64 [0.60-0.69] in the VATS group. Regarding the calibration, the Hosmer-Lemeshow test was not significant for both groups but more positive (better calibrated) for the VATS group (P = 0.12) compared to the RATS group (P = 0.08). CONCLUSIONS: The ECS seems applicable for patients operated with RATS, with a correct discrimination but a lower calibration performance for patients operated with VATS. A new score could be developed to specifically anticipate conversion in patients operated on by RATS.

Determinants of adherence and consequences of the transition from adolescence to adulthood among young people with severe haemophilia (TRANSHEMO): A multicentric French national observational cross-sectional study based on the FranceCoag registry.

INTRODUCTION: It is necessary to gain insights into adherence to healthcare in people with severe haemophilia (PwSH), especially during the transition from paediatric to adult care, which is an important phase in lives of young people with childhood chronic disease. This adherence can be considered as a marker of successful transition. OBJECTIVES: The main objective of the quantitative phase of the TRANSHEMO project was to compare the adherence to healthcare between adolescents and young adults (YAs) with severe haemophilia. The secondary objective was to identify the determinants (facilitators and barriers) of this adherence and associations between these determinants. METHODS: A multicentre, observational, cross-sectional study was conducted in 2017-2019 on PwSH aged between 14 and 17 years (adolescents) or between 20 and 29 years (YAs), included in the FranceCoag registry and having completed the questionnaires. The adherence to healthcare (treatment regimens and clinical follow-up) was compared between adolescents and YAs using the chi-squared test. The determinants of this adherence were analysed by structural equation modelling. RESULTS: There were 277 participants, 107 adolescents, and 170 YAs. The rate of adolescents adhering to healthcare was 82.2%, while the rate of YAs was 61.2% (p < .001). The barriers to the adherence to healthcare were being YA, having repeated at least one school grade and presenting mental health concerns. CONCLUSION: Adolescents had better adherence to healthcare than YAs. According to the determinants enlightened in this project, targeted supportive strategies and adapted therapeutic education programs can be developed for young PwSH to facilitate their adherence to healthcare.

Untargeted Multiomics Approach Coupling Lipidomics and Metabolomics Profiling Reveals New Insights in Diabetic Retinopathy.

Diabetic retinopathy (DR) is a microvascular complication of diabetes mellitus (DM) which is the main cause of vision loss in the working-age population. Currently known risk factors such as age, disease duration, and hemoglobin A1c lack sufficient efficiency to distinguish patients with early stages of DR. A total of 194 plasma samples were collected from patients with type 2 DM and DR (moderate to proliferative (PDR) or control (no or mild DR) matched for age, gender, diabetes duration, HbA1c, and hypertension. Untargeted lipidomic and metabolomic approaches were performed. Partial-least square methods were used to analyze the datasets. Levels of 69 metabolites and 85 lipid species were found to be significantly different in the plasma of DR patients versus controls. Metabolite set enrichment analysis indicated that pathways such as metabolism of branched-chain amino acids (methylglutaryl carnitine p = 0.004), the kynurenine pathway (tryptophan p < 0.001), and microbiota metabolism (p-Cresol sulfate p = 0.004) were among the most enriched deregulated pathways in the DR group. Moreover, Glucose-6-phosphate (p = 0.001) and N-methyl-glutamate (p < 0.001) were upregulated in DR. Subgroup analyses identified a specific signature associated with PDR, macular oedema, and DR associated with chronic kidney disease. Phosphatidylcholines (PCs) were dysregulated, with an increase of alkyl-PCs (PC O-42:5 p < 0.001) in DR, while non-ether PCs (PC 14:0-16:1, p < 0.001; PC 18:2-14:0, p < 0.001) were decreased in the DR group. Through an unbiased multiomics approach, we identified metabolites and lipid species that interestingly discriminate patients with or without DR. These features could be a research basis to identify new potential plasma biomarkers to promote 3P medicine.

Chorionicity and neurodevelopmental outcomes at 5½ years among twins born preterm: the EPIPAGE2 cohort study.

OBJECTIVE: To compare the neurodevelopmental outcomes of preterm twins at 5½ years by chorionicity of pregnancy. DESIGN: Prospective nationwide population-based EPIPAGE2 (Etude Epidémiologique sur les Petits Âges Gestationnels) cohort study. SETTING: A total of 546 maternity units in France, between March and December 2011. POPULATION: A total of 1126 twins eligible for follow-up at 5½ years. METHODS: The association of chorionicity with outcomes was analysed using multivariate regression models. MAIN OUTCOME MEASURES: Survival at 5½ years with or without neurodevelopmental disabilities (comprising cerebral palsy, visual, hearing, cognitive deficiency, behavioural difficulties or developmental coordination disorders) were described and compared by chorionicity. RESULTS: Among the 1126 twins eligible for follow-up at 5½ years, 926 (82.2%) could be evaluated: 228 monochorionic (MC) and 698 dichorionic (DC). Based on chronicity and gestational age of birth, we found no significant differences for severe neonatal morbidity. The rates of moderate/severe neurobehavioral disabilities were similar in infants from DC pregnancies versus infants from MC pregnancies (OR 1.22, 95% CI 0.65-2.28). By gestational age and without twin-twin transfusion syndrome (TTTS), no difference according to chorionicity was found for all neurodevelopmental outcome measures. CONCLUSIONS: The neurodevelopmental outcomes among preterm twins at 5½ years is similar, irrespective of chorionicity.

Impact of cardiac surgical timing on the neurodevelopmental outcomes of newborns with Complex congenital heart disease (CHD).

Background: More than half of infants with complex congenital heart disease (CHD) will have a neurodevelopmental disorder of multifactorial causes. The preoperative period represents a time-window during which neonates with complex CHD are in a state of hypoxia and hemodynamic instability, which fosters the emergence of brain injuries and, thus, affects early brain networks and neurodevelopmental outcomes. Currently, there is no consensus regarding the optimal age for cardiac surgery in terms of neurodevelopmental outcomes, and its definition is a real challenge. Our aim is to determine the relationship between cardiac surgical timing and long-term neurodevelopmental outcomes for various types of complex CHD. Methods: We hypothesize that earlier surgical timing could represent a neuroprotective strategy that reduces perioperative white matter injuries (WMIs) and postoperative morbidity, leading to improved neurodevelopmental outcomes in infants with complex CHD. Firstly, our prospective study will allow us to determine the correlation between age at the time of surgery (days of life) and neurodevelopmental outcomes at 24 months. We will then analyze the correlation between age at surgery and (i) the incidence of WMIs (through pre- and postoperative MRIs), (ii) postoperative morbidity, and (iii) the duration of the hospital stay. Implications and Dissemination: This research protocol was registered in the Clinical Trial Registry (National Clinical Trial: NCT04733378). This project aims to help launch the first Neurocardiac Investigation Clinic in Marseille - AP-HM - to propose an overall personalized monitoring and treatment program for patients operated on for complex CHD.

Reintervention of Residual Aortic Dissection after Type A Aortic Repair: Results of a Prospective Follow-Up at 5 Years.

Background After a type A aortic dissection repair, a patent false lumen in the descending aorta is the most common situation encountered, and is a well-known risk factor for aortic growth, reinterventions and mortality. The aim of this study was to analyze the long-term results of residual aortic dissection (RAD) at a high-volume aortic center with prospective follow-up. Methods In this prospective single-center study, all patients operated for type A aortic dissection between January 2017 and December 2022 were included. Patients without postoperative computed tomography scans or during follow-up at our center, and patients without RAD were excluded. The primary endpoint was all-cause mortality during follow-up for patients with RAD. The secondary endpoints were perioperative mortality, rate of distal aneurysmal evolution, location of distal aneurysmal evolution, rate of distal reinterventions, outcomes of distal reinterventions, and aortic-related death during follow-up. Results In total, 200 survivors of RAD comprised the study group. After a mean follow-up of 27.2 months (1-66), eight patients (4.0%) died and 107 (53.5%) had an aneurysmal progression. The rate of distal reintervention was 19.5% (39/200), for malperfusion syndrome in seven cases (3.5%) and aneurysmal evolution in 32 cases (16.0%). Most reinterventions occurred during the first 2 years (82.1%). Twenty-seven patients were treated for an aneurysmal evolution of RAD including aortic arch with hybrid repair in 21 cases and branched aortic arch endoprosthesis in six cases. In the hybrid repair group, there was no death, and the rate of morbidity was 28.6% (6/21) (one minor stroke, one pulmonary complication, one recurrent paralysis with complete recovery and three major bleeding events). In the branched endograft group, there was no death, no stroke, and no paraplegia. There was one case (16.7%) of carotid dissection. Complete aortic remodeling or complete FL thrombosis on the thoracic aorta was found in 18 cases (85.7%) and in five cases (83.3%) in the hybrid and branched endograft groups, respectively. Conclusions: Despite a critical course in most cases of RAD, with a high rate of aneurysmal evolution and reintervention, the long-term mortality rate remains low with a close follow-up and a multidisciplinary management in an expert center.

Prognostic value of forward flow indices in primary mitral regurgitation due to mitral valve prolapse.

Background: Degenerative mitral regurgitation (DMR) due to mitral valve prolapse (MVP) is a common valve disease associated with significant morbidity and mortality. Timing for surgery is debated for asymptomatic patients without Class I indication, prompting the search for novel parameters of early left ventricular (LV) systolic dysfunction. Aims: To evaluate the prognostic impact of preoperative forward flow indices on the occurrence of post-operative LV systolic dysfunction. Methods: We retrospectively included all consecutive patients with severe DMR due to MVP who underwent mitral valve repair between 2014 and 2019. LVOTTVI, forward stroke volume index, and forward LVEF were assessed as potential risk factors for LVEF <50% at 6 months post-operatively. Results: A total of 198 patients were included: 154 patients (78%) were asymptomatic, and 46 patients (23%) had hypertension. The mean preoperative LVEF was 69 ± 9%. 35 patients (18%) had LVEF ≤ 60%, and 61 patients (31%) had LVESD ≥40 mm. The mean post-operative LVEF was 59 ± 9%, and 21 patients (11%) had post-operative LVEF<50%. Based on multivariable analysis, LVOTTVI was the strongest independent predictor of post-operative LV dysfunction after adjustment for age, sex, symptoms, LVEF, LV end systolic diameter, atrial fibrillation and left atrial volume index (0.75 [0.62-0.91], p < 0.01). The best sensitivity (81%) and specificity (63%) was obtained with LVOTTVI ≤15 cm based on ROC curve analysis. Conclusion: LVOTTVI represents an independent marker of myocardial performance impairment in the presence of severe DMR. LVOTTVI could be an earlier marker than traditional echo parameters and aids in the optimization of the timing of surgery.

Early humoral response to COVID-19 vaccination in patients living with obesity and diabetes in France. The COVPOP OBEDIAB study with results from the ANRS0001S COV-POPART cohort.

BACKGROUND: Patients with diabetes and obesity are populations at high-risk for severe COVID-19 outcomes and have shown blunted immune responses when administered different vaccines. Here we used the 'ANRS0001S COV-POPART' French nationwide multicenter prospective cohort to investigate early humoral response to COVID-19 vaccination in the sub-cohort ('COVPOP OBEDIAB') of patients with obesity and diabetes. METHODS: Patients with diabetes (n = 390, type 1 or 2) or obesity (n = 357) who had received two vaccine doses and had no history of previous COVID-19 infection and negative anti-nucleocapsid (NCP) antibodies were included and compared against healthy subjects (n = 573). Humoral response was assessed at baseline, at one month post-first dose (M0) and one-month post-second dose (M1), through percentage of responders (positive anti-spike SARS-CoV-2 IgG antibodies (Sabs), geometric means of Sabs; BAU/mL), proportion of individuals with anti-RBD antibodies, and proportion of individuals with anti-SARS-CoV-2-specific neutralizing antibodies (Nabs). Potential clinical and biological factors associated with weak response (defined as Sabs < 264 BAU/mL) and presence of non-reactive anti-RBD antibodies at M1 were evaluated. Univariate and multivariate regressions were performed to estimate crude and adjusted coefficients with 95 % confidence intervals. Poor glycemic control was defined as HbA1c ≥ 7.5 % at inclusion. RESULTS: Patients with diabetes, particularly type 2 diabetes, and patients with obesity were less likely to have positive Sabs and anti-RBD antibodies after the first and second dose compared to controls (p < 0.001). At M1, we found Sabs seroconversion in 94.1 % of patients with diabetes versus 99.7 % in controls, anti-RBD seroconversion in 93.8 % of patients with diabetes versus 99.1 % in controls, and Nabs seroconversion in 95.7 % of patients with diabetes versus 99.6 % in controls (all p < 0.0001). Sabs and anti-RBD seroconversion at M0 and M1 were also significantly lower in obese patients than controls, at respectively 82.1 % versus 89.9 % (p = 0.001; M0 Sabs), 94.4 % versus 99.7 % (p 0.001; M1 Sabs), 79.0 % vs 86.2 % (p = 0.004 M0 anti-RBD), and 96.99 % vs 99.1 % (p = 0.012 M1 anti-RBD). The factors associated with low vaccine response (BAU < 264/mL) in patients with diabetes were chronic kidney disease (adjusted OR = 6.88 [1.77;26.77], p = 0.005) and poor glycemic control (adjusted OR = 3.92 [1.26;12.14], p = 0.018). In addition, BMI ≥ 40 kg/m2 was found to be associated with a higher vaccine response (adjusted OR = 0.10 [0.01;0.91], p = 0.040) than patients with BMI < 40 kg/m2. CONCLUSION: COVID-19 vaccine humoral response was lower in patients with obesity and diabetes one month after second dose compared to controls, especially in diabetic patients with CKD or inadequate glycemic control. These findings point to the need for post-vaccination serological checks in these high-risk populations.

Incidence of Persistent Left Bundle Branch Block After Rapid-Deployment Aortic Valve Replacement.

BACKGROUND: We evaluated the incidence, prognosis, and predictive factors of new onset of persistent left bundle branch block (NOP-LBBB) after rapid-deployment aortic valve replacement (RD-AVR). METHODS: This was an observational, retrospective, single-center study of 274 consecutive patients with no baseline ventricular conduction disorder and no previous permanent pacemaker implantation (PPI) who underwent RD-AVR with an INTUITY valve (n = 55) or INTUITY Elite Valve (n = 219) (Edwards Lifesciences). Transthoracic echocardiography and 12-lead electrocardiography was performed preoperatively, at discharge, and at 1-month and 1-year intervals. The incidence, prognosis, and predictive factors of NOP-LBBB were evaluated. RESULTS: NOP-LBBB occurred in 58 patients (21.2%) after discharge. In multivariate analysis, age (P < .01), INTUITY valve diameter ≥23 mm (P = .02), and INTUITY Elite implantation (P = .01) were independent predictors of NOP-LBBB. By 1:1 propensity matching analysis between the NOP-LBBB group and the control group, there were no significant differences in 1-year overall mortality (P = .23), hospitalization for congestive heart failure (P = .99), or PPI (P = .99). NOP-LBBB exposed patients to a high rate of dysrhythmic events (12.1% vs 1.4%, P < .01) and was associated with a significant decrease in left ventricular ejection fraction (0.62 ± 0.095 vs 0.652 ± 0.0783, P = .02) without an impact on New York Heart Association functional status (1.25 ± 0.32 and 1.52 ± 0.70, P = .32). PPI was performed in 17 patients (6.2%) before discharge, including 14 NOP-LBBB patients. CONCLUSIONS: NOP-LBBB after RD-AVR is prevalent in patients with no prior conduction disorders. INTUITY Elite is associated with a significantly higher rate of NOP-LBBB. The persistence of NOP-LBBB predisposed patients to the occurrence of high-grade conduction disorders and might have led to PPI but did not increase death or hospitalization for congestive heart failure.

Individual and Family Determinants for Quality of Life in Parents of Children with Inborn Errors of Metabolism Requiring a Restricted Diet: A Multilevel Analysis Approach.

OBJECTIVE: The objective of this study was to compare the quality of life (QoL) for parents of children with inborn errors of metabolism (IEMs) requiring a restricted diet with French population norms and investigate parental QoL determinants. STUDY DESIGN: This cross-sectional study included mothers and/or fathers of children < 18 years of age affected by IEMs requiring a restricted diet (except phenylketonuria) from January 2015 to December 2017. Parents' QoL was assessed using the World Health Organization Quality of Life BREF questionnaire and compared with age- and sex-matched reference values from the French general population. Linear mixed models were used to examine the effects of demographic, socioeconomic, disease-related, and psychocognitive factors on parental QoL, according to a 2-level regression model considering individuals (parents) nested within families. RESULTS: Of the 1156 parents invited to participate, 785 (68%) were included. Compared with the general population, parents of children with IEMs requiring a restricted diet reported a lower QoL in physical and social relationship domains but a higher QoL in the psychological domain. In the multivariate analysis, characteristics associated with poorer parental QoL included both parent-related factors (being a father, older age, more educated parent, nonworking parent, greater anxiety, seeking more social support, and using less positive thinking and problem-solving coping strategies) and family-related factors (disease complications, increased number of hospital medical providers, child's younger age, single-parent family, and lower family material wealth). CONCLUSION: Parents of children with IEMs requiring a restricted diet reported poorer QoL in physical and social relationship domains than population norms. Psychocognitive factors, beyond disease-specific and family-related characteristics, were the most important determinants influencing parental QoL and may represent essential aspects for interventions. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov: NCT02552784.

Real-life clinical impact of a five-tiered classification of pituitary tumors.

Introduction: Usually benign, pituitary tumors (PT) can be invasive and aggressive with a propensity to progress and/or recur. Trouillas's clinicopathological classification attempts to predict the evolutionary risk of a PT. In this study, we assessed the prognostic value of this classification in an independent patient cohort and analyzed its impact on treatment strategies. Patients and methods: In this study, 607 patients operated on between 2008 and 2018 for a PT were included. Grading was established based on invasion, proliferative activity (Ki-67, mitotic index) and p53 positivity. The therapeutic management following surgery was analyzed. Progression-free survival (PFS) of the graded tumors was estimated (Kaplan-Meier method and log-rank test) and a multivariate analysis was performed (Cox regression model). Results: Grading identified non-invasive PT without (grade 1a: 303 cases) or with proliferative activity (grade 1b: 53 cases) and invasive PT without (grade 2a: 202 cases) or with proliferative activity (grade 2b: 49 cases). The mean follow-up was 47 ± 30 months (median: 38 months). Progression/recurrence occurred in 127 cases. Grades were significant and independent predictors of PFS (P < 0.001) with a 4.8-fold higher risk of progression/recurrence in grade 2b as compared to grade 1a. As second-line therapy, gamma knife or conventional radiotherapy controlled tumor growth in 91.6 and 100% of cases, respectively, irrespective of the grade. Proliferative tumors exposed the patient to a 9.5-fold higher risk of having ≥3 adjuvant therapeutic lines as compared to non-proliferative tumors. Discussion: Grading of a PT according to Trouillas's classification predicts its risk of progression and should advocate for a personalized therapeutic approach in invasive and proliferative tumors. Significance statement: This is the first study to assess, on a cohort of 607 well-characterized patients, the real-life therapeutic impact of the five-tiered clinicopathological classification of pituitary tumors. First, we validate that pituitary tumor grades predict the evolutionary risk of the tumor, with a significant higher risk of progression/recurrence in invasive and/or proliferative tumors (mean follow-up: 47 ± 30 months, median: 38 months). Moreover, our study provides evidence that patients with proliferative tumors have a higher risk to be retreated after primary surgery and point toward the fact that radiotherapy can successfully control tumor growth in case of progression or recurrence. Our findings advocate for a personalized therapeutic approach in clinically aggressive pituitary tumors.

Occupational integration of adults with severe haemophilia (INTHEMO): A study based on the FranceCoag registry.

INTRODUCTION: Health of people with severe haemophilia (PwSH) improves thanks to the advancements in haemophilia care, giving them more opportunities in occupational integration. However, there is little literature on the occupational integration of PwSH. OBJECTIVES: The main objective of our study was to assess the occupational integration of PwSH and to compare it with that of the general population. The secondary objective was to study the association between individual characteristics (sociodemographic, clinical and psycho-behavioural) and occupational integration of PwSH. METHODS: A multicentre, non-interventional, cross-sectional study was conducted in 2018-2020 on PwSH, aged over 18 and under 65 years and included in the FranceCoag registry. Measurements included indicators of occupational integration, sociodemographic, clinical and psycho-behavioural characteristics. The indicators of occupational integration were compared with those of the general population, using indirect standardization. The data of the general population were available from the National Institute of Statistics and Economic Studies (INSEE). Determinants of occupational integration were explored using structural equation modelling. RESULTS: Of 1262 eligible people, 588 were included. PwSH had a lower employment rate than the general population (standardized ratio, .85; 95% CI, .77-.94). There were more PwSH at tertiary education level than expected (standardized ratio, 1.38; 95% CI, 1.17-1.61). HIV infection, poor physical health and mental health concerns were associated with a higher risk of unemployment in PwSH. CONCLUSION: Employment rate of PwSH is lower than that of the general population despite their higher education level. Target interventions focusing on determinants of difficult occupational integration could be helpful for PwSH.

Presence of specific SARS-COV2 antibodies in hemodialysis patients and their caregivers after the first wave of COVID-19.

Hemodialysis (HD) patients are at risk for severe COVID-19 and cannot comply with social distancing. SARS-COV2 seroprevalence in French patients and caregivers after the first wave of COVID-19 is unknown. SeroCOVIDial is a prospective study conducted between June and December 2020. SARS-COV2 seroprevalence was evaluated by a rapid serological test (BIOSYNEX) in HD patients and caregivers, and the presence or not of anti-SARS-COV2 neutralizing or non-neutralizing antibodies in patients was also determined by ELISA and seroneutralization. In June 2020, 451 HD patients and 238 caregivers were included. Overall SARS-COV2 seroprevalence was 8.4% (patients) and 6.7% (caregivers), and was 87.1% (patients) and 90.0% (caregivers) in participants with a previously documented SARS-COV2 infection. Overall seroprevalence reached 13.8% (patients) and 12.6% (caregivers) following the second epidemic wave. During the follow-up, 38 (8.4%) patients died (9 of COVID-19). Among the 44 (10.6%) patients who became infected, only two were seropositive at M0. The levels of anti-SARS-COV2 antibodies decreased over time in patients and caregivers. The BIOSYNEX test showed 82.9% sensitivity and 97.7% specificity. Prevalence of anti-SARS-COV2 antibodies was low in HD patients and caregivers after the first epidemic wave but rose after the second wave. A rapid serological test showed good performances and could be useful for future monitoring of anti-SARS-COV2 antibodies.

Long Term Neurodevelopmental Outcomes after Sevoflurane Neonatal Exposure of Extremely Preterm Children: A Cross-Sectional Observationnal Study.

Sevoflurane, a volatile anesthetic, is used when extremely preterm neonates (EPT) undergo painful procedures. Currently, no existing studies analyze sevoflurane's long-term effects during the EPT's immediate neonatal period. Our primary objective was to compare the EPT's neurocognitive development regardless of any sevoflurane exposure prior to 45 weeks corrected gestational age (GA). We analyzed those live discharges, less than 28 weeks GA, who were either exposed, unexposed, and/or multiply exposed to sevoflurane before 45 weeks GA. All data were obtained from a cross-sectional multicenter study (GPQoL study, NCT01675726). Children, both exposed and non-exposed to sevoflurane, were sampled using a propensity-guided approach. Neurological examinations (Touwen), cognitive and executive functions (WISC IV, NEPSY, Rey figure), and assessments when the children were between 7 and 10 years old, were correlated to their neonatal sevoflurane exposure. There were 139 children in the study. The mean gestational age was 26.2 weeks (±0.8) GA and the mean birth weight was 898 g (±173). The mean age of their evaluation was 8.47 years old (±0.70). Exposure to sevoflurane to the mean corrected age 27.10 (3.37) weeks GA had a significant correlation with cerebral palsy (adjusted odds ratio (aOR): 6.70 (CI 95%: 1.84-32.11)) and other major disorders (cerebral palsy and/or severe cognitive retardation) (aOR: 2.81 [95% CI: 1.13-7.35]). Our results demonstrate the possibility of long-term effects on EPT infants who had a sevoflurane exposure before 45 weeks corrected GA. However, these results will require further confirmation by randomized controlled trials.

Is Oxidative Stress an Emerging Player in the Thrombosis of Patients with Anti-Phosphatidylethanolamine Autoantibodies?

The detection of anti-phosphatidylethanolamine autoantibodies (aPEs) has been proposed to improve the diagnosis and management of patients presenting clinical manifestations of antiphospholipid syndrome (APS), such as thrombosis, and who are persistently negative for conventional markers. After selecting the most specific ELISA for their detection, we evidenced the interest of aPEs in the exploration of thrombosis when APS conventional markers were negative through a 1-year retrospective study including 1131 consecutive patients routinely tested for aPEs. To validate this result, we assessed aPEs in a newly selected population of 77 patients with unexplained deep vein thrombosis (DVT). With a total prevalence of 19.5%, we confirmed the interest of aPE detection in patients with unexplained DVT who were devoid of other aPLs markers. Since endosomal compartment, a source of ROS production, has been recently identified as the cellular target of aPEs in vitro, we then investigated an association between aPE positivity and reactive oxygen species (ROS) production by measuring the production of thiobarbituric acid-reactive substances. We showed, for the first time, a significant association between aPE positivity and systemic ROS production in patients which led us to hypothesize a new mechanism of action of aPEs in thrombosis through a signaling related to oxidative stress.

Metoclopramide Test in Hyperprolactinemic Women With Polycystic Ovarian Syndrome: Old Wine Into New Bottles?

INTRODUCTION: Polycystic ovarian syndrome (PCOS) is the most frequent etiology of anovulation, hyperandrogenism and infertility in women. Its pathophysiology remains poorly elucidated. Hyperprolactinemia (hPRL) is common in women of reproductive age and may partially mimic the clinical phenotype of PCOS. The simultaneous finding of both conditions is therefore not rare, however there are conflicting studies on whether a link exists between them. MATERIALS AND METHODS: We conducted a retrospective monocentric study between 2015 and 2021 and among women who were referred for possible PCOS, we selected those who met the ESHRE/Rotterdam definition criteria. hPRL was defined as two values above the upper limit of normal with at least one measurement in our centre. RESULTS: A total of 430 women were selected, of whom 179 met the PCOS criteria. 50 out of 179 patients (27.9%) had at least one elevated value of PRL and 21 (11.7%) had hPRL according to our definition. Among the 21 women of the PCOS/hPRL cohort, 5 (23.8%) had a microprolactinoma and all of them had PRL level ≥ 60 ng/ml. The remaining cases were macroprolactinemia (n=5), iatrogenic hPRL (n=4), primary hypothyroidism (n=1) or unexplained (n=6) despite exhaustive investigations. The metoclopramide test resulted in an increase of basal PRL < 300% in all prolactinomas and ≥ 300% in all the other etiologies. CONCLUSION: hPRL was a common finding in PCOS women, secondary to a microprolactinoma in a quarter of cases. Metoclopramide test performed in women with hPRL below 60 ng/ml appeared as a helpful tool 1) to discriminate pituitary causes from others etiologies, 2) to potentially avoid unnecessary pituitary MRI.