Introduction The optimal method for removing the endotracheal tube (ETT) during extubation in the intensive care unit (ICU) remains uncertain. Two methods are described for removing the ETT in ICU, namely the ‘Traditional technique’ with continuous aspiration during cuff deflation and ETT removal; and the ‘PEEP’ method, which consists in applying positive end-expiratory pressure (PEEP) before and during cuff deflation and ETT removal. Our hypothesis is that applying PEEP during extubation in the ICU would improve clinical outcome.Methods and analysis This is a prospective, multicentre, randomised, open-label, controlled, superiority trial, analysed by intention-to-treat, comparing ETT removal with concomitant suction vs application of PEEP before and during ETT removal. In total, 424 patients will be recruited and randomly assigned in a 1:1 ratio to one of two groups, according to the strategy of ETT removal. The primary outcome is the number of days free from any mechanical ventilation within 28 days following extubation. Secondary outcomes include the reintubation rate up to 7 days after ETT removal, the cumulative duration of non-invasive ventilation up to 7 days following extubation, the rate of acute respiratory failure, the rate of acquired pneumonia during the first 7 days following ETT removal, the length of stay in ICU and in hospital and all-cause mortality at 28 days following ETT removal.Ethics and dissemination The study was approved by the Ethics Committee ‘CPP Ile de France II’. Patients will be included after providing written informed consent. The results will be submitted for publication in peer-reviewed journals, and in national and international congresses.Trial registration number NCT05147636.

The Findable, Accessible, Interoperable, and Reusable guiding principles promote Findability, Accessibility, Interoperability, and Reuse of data to enhance data management and stewardship. In biomedicine, particular ethical, legal, and technical barriers complicate research data sharing. To help researchers overcome these challenges, we propose a framework of FAIRification from three dimensions - scientific, technical, and legal/ethical. We advocate for prospective FAIRification of study data, starting with a strong emphasis on planning for data-sharing from the beginning. Reflective questions throughout the process guide researchers to reflect on their situation. Researchers should assess resources and feasibility, secure technical and legal support, consider stakeholder needs, and devise an appropriate data sharing process. Given the sensitivity of biomedical data, confidentiality and security require careful attention. The data sharing strategy should be finalized before the study starts and documented in relevant study materials. Technical preparation for data sharing follows planning. Data should be well-documented with a data dictionary and metadata to facilitate reuse and provided in an accessible format. The data can be hosted on a repository to promote sharing and reuse. While a secure repository provides the technical foundation for data protection, effective administration is required to enforce data use agreements and licensing. We also discuss the importance of subsequent management upon data upload. Continued support for researchers and data maintenance are essential for effective reuse. Examples and resources to facilitate FAIRification are included to help researchers navigate challenges and ensure biomedical data are FAIR and reusable.

BACKGROUND:In patients with moderate-to-severe acute respiratory distress syndrome, the frequency of pressure ulcers is higher in the prone position than in the supine position. AIM:To assess the effect of a bundle of interventions to prevent pressure ulcers in patients with acute respiratory distress syndrome prone. STUDY DESIGN:ESCARD is a stepped-wedge prospective multicentre trial conducted in France that included patients with moderate-to-severe acute respiratory distress syndrome, intubated and with an indication for pronation. In the control period, patients received the routine means of each centre. In the experimental period, the bundle of specific standardized means included: eye protection with methylcellulose; strapped lower eyelids; 15° body inclination; specific cushions inserted between the mattress and head/thorax and knees/feet; head rotation every 4 h. The primary end-point was the occurrence of a new pressure ulcer at any location and stage in the anterior part of the body 7 days after inclusion. It was assessed from pictures taken in the supine position and independently analysed by two experts blinded to the allocated period. RESULTS:From 16 April 2018 to 3 December 2020 (with an interruption between 12 March and 15 July 2020 because of COVID pandemic), a total of 160 patients were included in 9 centres; 156 were analysed. At the first proning session, all 6 specific preventive means were implemented in 1.2% of the patients in the control period and 91.8% in the experimental period. At Day 7, 53 patients (63.9%) in the control versus 40 (54.8%) in the experimental period had a new pressure ulcer at any location and of any stage (odds ratio = 0.92; 95% confidence interval [0.39; 2.18]). There was a 42.8% discrepancy between the two experts. CONCLUSIONS:In this prospective multicentre stepped-wedge trial, the bundle of interventions did not lead to a significant reduction in the frequency of new pressure ulcers in moderate-to-severe acute respiratory distress syndrome patients treated by prone position. RELEVANCE TO CLINICAL PRACTICE:The critical care nurses were able to manage patients enrolled in a complex trial up to its planned end. Even though negative, the study should encourage intensive care unit (ICU) nurses to better define the bundle of interventions including introducing other methods not used in the present study. ICU nurses should also assess the stage of pressure ulcers consistently over time. ICU nurses should consider further studies because pressure ulcer is a relevant issue of concern during the pronation in acute respiratory distress syndrome patients. If so, the new trial should include a larger number of ICUs. TRIAL REGISTRATION:The protocol was approved by an ethics committee (number 2017-A01449-44 on 7 October 2017) and was recorded in clinicaltrials.gov (NCT03125421).

Background: Hereditary haemorrhagic telangiectasia (HHT) is a genetic vascular disorder characterised by telangiectases, which cause nasal and gastrointestinal (GI) bleeding, and visceral arteriovenous malformations. Since 2012 bevacizumab, a monoclonal antibody targeting vascular endothelial growth factor, has been a promising treatment for HHT-related bleeding and was evaluated in the phase II BABH study. Objective: To follow and describe evolution and treatments of patients with HHT post-BABH study. Design: This study is a 1-year, multi-centre descriptive study. Methods: We collected clinical (nose and GI bleeding, red blood cell transfusions) and biological (haemoglobin and ferritin levels) data and treatment information. Results: Of 22 patients included across 4 centers, 15 received bevacizumab. Among them, 12 (86%) had a >50% decrease in the number of RBC units transfused 3 months post-treatment. Mean haemoglobin levels increased from 83.08 to 105.98 g/L. Conclusion: Bevacizumab effectively reduces RBC transfusions and is efficient for treating severe bleeding in patients with HHT. Trial registration: This trial was registered with the ClinicalTrials.gov Identifier #NCT06039124.

Epistaxis greatly affects patients with hereditary hemorrhagic telangiectasia (HHT). Although few systemic treatment exist, nintedanib, is a good candidate thanks to its anti-angiogenic activity. Our main objective was to evaluate the efficacy of oral nintedanib on epistaxis duration in HHT patients with moderate to severe epistaxis. This multicenter phase 2 randomized, placebo-controlled, double-blind trial was conducted between June 2020 and February 2023. Inclusion criteria were being over 18 years old and having a confirmed HHT diagnosis with an epistaxis severity score greater than 4. Sixty patients were randomized to receive either nintedanib or placebo for 12 weeks with a 12 week follow-up. The primary endpoint was the proportion of patients achieving a reduction of at least 50

BackgroundBoth hereditary haemorrhagic telangiectasia (HHT) and juvenile polyposis syndrome (JPS) are known to be caused bySMAD4pathogenic variants, with overlapping symptoms for both disorders in some patients. Additional connective tissue disorders have also been reported. Here, we describe carriers ofSMAD4variants followed in an HHT reference centre to further delineate the phenotype.MethodsObservational study based on data collected from the Clinical Investigation for the Rendu-Osler Cohort database.ResultsThirty-three participants from 15 families, out of 1114 patients with HHT, had anSMAD4variant (3%).Regarding HHT, 26 out of 33 participants (88%) had a definite clinical diagnosis based on Curaçao criteria. Complication frequencies were as follows: epistaxis (n=27/33, 82%), cutaneous telangiectases (n=19/33, 58%), pulmonary arteriovenous malformations (n=17/32, 53%), hepatic arteriovenous malformations (AVMs) (n=7/18, 39%), digestive angiodysplasia (n=13/22, 59%). No cerebral AVMs were diagnosed.Regarding juvenile polyposis, 25 out of 31 participants (81%) met the criteria defined by Jasset alfor juvenile polyposis syndrome. Seven patients (21%) had a prophylactic gastrectomy due to an extensive gastric polyposis incompatible with endoscopic follow-up, and four patients (13%) developed a digestive cancer.Regarding connective tissue disorders, 20 (61%) had at least one symptom, and 4 (15%) participants who underwent echocardiography had an aortic dilation.ConclusionWe describe a large cohort ofSMAD4variant carriers in the context of HHT. Digestive complications are frequent, early and diffuse, justifying endoscopy every 2 years. The HHT phenotype, associating pulmonary and hepatic AVMs, warrants systematic screening. Connective tissue disorders broaden the phenotype associated withSMAD4gene variants and justify systematic cardiac ultrasound and skeletal complications screening.

Physical activity (PA), has a proven effect on overall health. The study assessed the difference in glomerular filtration rate (GFR) over one year in non-dialysis renal failure patients between those who practiced exercise (P) and those who did not (NP). Patients were categorised as P or not P using the Global Physical Activity Questionnaire (GPAQ2), completed by telephone, at inclusion and at 12 months. Among the 259 patients included, 195 (75.3%) practiced a PA and 64 (24.7%) did not practiced. There was no significant difference in the slope of GFR decline from inclusion to month 12 between the two groups, p = 0.4107. Only the type of kidney seemed to be significantly associated with the slope of GFR decline over the 12 months (p = 0.0039). These results may be explained by a follow-up time too short to identify an effect of behavioural change on the progression of kidney disease.L’activité physique (AP) a un effet démontré sur l’état de santé global. L’étude évaluait, chez des patients insuffisants rénaux non dialysés, la différence, sur un an, de l’évolution du débit de filtration glomérulaire (eDFG) entre ceux pratiquant une AP (P) et ceux n’en pratiquant pas (NP). Les patients ont été classés comme P ou NP grâce au questionnaire d’AP GPAQ2, passé par téléphone, à l’inclusion et à 12 mois. Parmi les 259 patients inclus, 195 (75,3 %) pratiquaient une AP et 64 (24,7 %) n’en pratiquaient pas. Il n’existe pas de différence significative sur la pente de décroissance du eDFG entre l’inclusion et le 12e mois (p = 0,4107). Le type de néphropathie semblerait associé significativement à cette pente de décroissance au cours des 12 mois (p = 0,0039). Ces résultats peuvent s’expliquer par une durée de suivi trop courte pour mettre en évidence un effet de la modification du comportement sur l’évolution de la maladie rénale.

Bevacizumab—a humanized monoclonal antibody—has been widely used to treat patients with hereditary hemorrhagic telangiectasia (HHT), but no randomized trial has yet been conducted. This study is a double-blind multicenter randomized phase 2 trial with a 1:1 active-treatment-to-placebo ratio. We included patients over the age of 18 with a confirmed diagnosis and the need for at least four red blood cell (RBC) units transfused in the 3 months before study enrollment. Bevacizumab was administered at a dose of 5 mg/kg every 14 days with a total of six injections. The primary efficacy criterion was a decrease of at least 50% in the cumulative number of RBC units transfused in a 3-month period before and after treatment. A total of 24 patients (12 in each group) were included and randomized at 4 different centers. In intention-to-treat analysis, 63.6% of patients (7/11) in the bevacizumab group versus 33.3% of patients (4/12) in the placebo group decreased the number of blood transfusions by at least 50% ( p  = 0.22). Hemoglobin levels significantly improved at 6 months in the bevacizumab versus placebo group ( p  = 0.02). The pharmacokinetics study revealed that patients with high exposure to bevacizumab had a significant decrease in RBC transfusions ( p  = 0.03). Fifty-nine adverse events were observed, 34 in the placebo arm versus 25 in the bevacizumab arm. Though the present trial was underpowered, patients with HHT receiving bevacizumab required numerically fewer red blood cell transfusions than those receiving placebo, particularly those with high exposure.

Physical activity (PA), has a proven effect on overall health. The study assessed the difference in glomerular filtration rate (GFR) over one year in non-dialysis renal failure patients between those who practiced exercise (P) and those who did not (NP). Patients were categorised as P or not P using the Global Physical Activity Questionnaire (GPAQ2), completed by telephone, at inclusion and at 12 months. Among the 259 patients included, 195 (75.3%) practiced a PA and 64 (24.7%) did not practiced. There was no significant difference in the slope of GFR decline from inclusion to month 12 between the two groups, p = 0.4107. Only the type of kidney seemed to be significantly associated with the slope of GFR decline over the 12 months (p = 0.0039). These results may be explained by a follow-up time too short to identify an effect of behavioural change on the progression of kidney disease.

Data sharing enhances the value of medical research and builds trust in clinical trials, but more biomedical researchers need to be trained in these approaches, which include meta-research, data science and ethical, legal and social issues.

Although the underrepresentation of women in publication is a proven fact, there is no information on its counterpart: retractions. Using a previously studied cohort of retractions, the gender of the first author was checked manually to see if there was a similar pattern in the reasons for retraction for women and men authors. Out of 120 retractions, gender was identified for 113 (94.2%). A total of 42 (37.2%) retractions concerned publications authored by women and the reasons for retraction were significantly different between men and women authors. Overall, fraud and plagiarism accounted for 28.6 and 59.2% of women and men-authored retractions, respectively. These findings may have implications as regards training in responsible conduct in research; however, without further investigating larger cohorts and a better understanding of underlying mechanisms, it would be premature to draw any firm conclusions at this stage.

Bevacizumab—a humanized monoclonal antibody—has been widely used to treat patients with hereditary hemorrhagic telangiectasia (HHT), but no randomized trial has yet been conducted.

Objective To retrospectively describe a large series of pregnancies in women with hereditary haemorrhagic telangiectasia followed in our reference centre, plus neonatal outcomes, to better understand the risks of complications and to improve their prevention. Design A retrospective descriptive study conducted through a phone questionnaire. Setting Reference centre for hereditary haemorrhagic telangiectasia in Lyon, France. Population Women meeting the following criteria: (1) alive and aged >= 18 years; (2) with a definite clinical and/or genetic diagnosis of hereditary haemorrhagic telangiectasia; and (3) with at least one full-term pregnancy. Main outcome measures Maternal and perinatal outcomes of pregnancies in women with hereditary haemorrhagic telangiectasia. Results Five hundred and sixty-two pregnancies were reported in 207 women with hereditary haemorrhagic telangiectasia. A total of 271 complications (48.2%) were registered. Of these, 149 (55%) non-specific complications, 110 (40.6%) non-severe specific complications and 12 (4.4%) severe specific complications were registered. There were four cases of haemoptysis and two cases of transient ischaemic attack related to pulmonary arteriovenous malformations. Four patients had severe decompensated dyspnoea, related to pulmonary arteriovenous malformations in three cases and to pulmonary arteriovenous malformations associated with severe hepatic arteriovenous malformations in one case. Hepatobiliary necrosis occurred in one case. Epidural or spinal anaesthesia was performed in 139 of 452 deliveries (31%), without complications. There were 12 reports of congenital anomalies in 461 live births (3%). Conclusions Most pregnancies in hereditary haemorrhagic telangiectasia women are uneventful; complications are rare but can be severe. Women thus need to be educated about screening and possible pregnancy-related risks before becoming pregnant.

Clinical trial data-sharing is seen as an imperative for research integrity and is becoming increasingly encouraged or even required by funders, journals, and other stakeholders. However, early experiences with data-sharing have been disappointing because they are not always conducted properly. Health data is indeed sensitive and not always easy to share in a responsible way. We propose 10 rules for researchers wishing to share their data. These rules cover the majority of elements to be considered in order to start the commendable process of clinical trial data-sharing: Rule 1: Abide by local legal and regulatory data protection requirementsRule 2: Anticipate the possibility of clinical trial data-sharing before obtaining fundingRule 3: Declare your intent to share data in the registration stepRule 4: Involve research participantsRule 5: Determine the method of data accessRule 6: Remember there are several other elements to shareRule 7: Do not proceed aloneRule 8: Deploy optimal data management to ensure that the data shared is usefulRule 9: Minimize risksRule 10: Strive for excellence.

Gender bias, widely investigated in science on positive aspects such as obtaining funding or publications, remains unexplored on the « negative » aspects of science such as bad academic practices: if women are less visible in science, are they less inclined to dishonest, reprehensible or condemnable behavior?

Helium is known to reduce airflow limitation. Our hypothesis was that severeCOPD patients undertaking exercise would show greater improvement in endurance under aheliox mixture (80/20%) than under air alone. This hypothesis was tested in a double-blinded, randomized study. Methods. - Out of the 53 patients included, 45 were randomly assigned to two groups : Heliox( n = 23) and Air (n = 22). Patients were assessed with spirometry under air and heliox, incrementalexercise test, constant workload (80% Wmax) exercise test and weekly 6-minute walk test. Thetwo groups went through fifteen 30-minute retraining sessions in the overall framework of anidentical pulmonary rehabilitation program. Results. - There was no significant difference in endurance improvement (Heliox : +52.5 sec, Air: + 114 sec, median value). FEV1 improvement under heliox exceeding 10% identified a groupof 20 patients as ``helium responders'', who improved their endurance time by a median of135 sec compared to 50 sec for the ``non-responders'' (non-significant difference). Conclusion. - In patients with severe COPD, use of Heliox in exercise retraining did not producesignificantly improved endurance. On the other hand, ``helium responders'' showed more FEV1improvement than non-responders. Improved FEV1 under heliox should therefore be used infuture studies as an inclusion criterion. (c) 2022 SPLF. Published by Elsevier Masson SAS. All rights reserved.

PURPOSE:To evaluate mean change in best-corrected visual acuity (BCVA) at 52 weeks in patients with inflammatory choroidal neovascularization (CNV) treated with aflibercept.METHODS:We conducted a prospective non-comparative open-label trial. Following one mandatory intravitreal injection of aflibercept, patients were treated under a pro re nata (PRN) dosing regimen with monthly visits.RESULTS:A total of 19 patients were included, but one presented exclusion criteria; 16 patients were followed for the whole 52-week study, and data for the primary endpoint analysis were available for 14. At baseline, mean BCVA and mean central retinal thickness (CRT) were 64.53 (±19.64) letters and 351.79 (±97.77) μm, respectively. At 52 weeks, the mean change in BCVA was +9.50 (±12.90) letters [95%CI = +2.05-+16.95]. One patient had lost more than 15-letters at 24 weeks, and another one at 52 weeks. CRT change was -62.77 (±100.73) μm at 24 weeks and -66.53 (±97.47) μm at 52 weeks. There was a mean number of 3.56 (±3.29) intravitreal injections at 52 weeks (min = 1; max = 12). No serious ocular adverse events related to the treatment were reported.CONCLUSIONS:Our study shows that aflibercept is clinically effective, both anatomically and functionally in the treatment of inflammatory CNV. Following the first injection, the PRN strategy appears sufficient for treating most choroidal neovessels.

Purpose Peritoneal carcinomatosis from appendiceal goblet cell carcinoma (A-GCC) is a rare and aggressive form of appendiceal tumor. Cytoreductive surgery (CRS) and hyperthermic intra peritoneal chemotherapy (HIPEC) was reported as an interesting alternative regarding survival compared to surgery without HIPEC and/or systemic chemotherapy. Our aim was to evaluate the impact of CRS and HIPEC for patients presenting A-GCC through an international registry. Methods A prospective multicenter international database was retrospectively searched to identify all patients with A-GCC tumor and peritoneal metastases who underwent CRS and HIPEC through the Peritoneal Surface Oncology Group International (PSOGI). The post-operative complications, long-term results, and principal prognostic factors were analyzed. Results The analysis included 83 patients. After a median follow-up of 47 months, the median overall survival (OS) was 34.6 months. The 3- and 5-year OS was 48.5% and 35.7%, respectively. Patients who underwent complete macroscopic CRS had a significantly better survival than those treated with incomplete CRS. The 5-year OS was 44% and 0% for patients who underwent complete, and incomplete CRS, respectively (HR 9.65, p < 0.001). Lymph node involvement and preoperative chemotherapy were also predictive of a worse prognosis. There were 3 postoperative deaths, and 30% of the patients had major complications. Conclusion CRS and HIPEC may increase long-term survival in selected patients with peritoneal metastases of A-GCC origin, especially when complete CRS is achieved. Ideally, randomized control trials or more retrospective data are needed to confirm CRS and HIPEC as the gold standard in this pathology.

We conducted two studies to investigate why academics accept to award a prestigious title for unsatisfactory Ph.D. dissertations. Through semi-structured interviews with 19 academics, the first study showed that convenience theses could either be planned as such from the beginning of the doctoral work or become so as the doctorate develops. In the second, scenario-based study (N = 89 academics), we found that the acceptability of obtaining a title of convenience depends on the career envisaged by the doctoral student and the specific shortcomings of the dissertation. On the one hand, the present research allows to discuss how the academics’ ethics of responsibility can supplant their ethics of conviction. On the other hand, it raises the question of the referential, which is not shared and allows for flexibility in requirements for delivering the Ph.D.

Introduction:The aim of the study was to assess the clinical reliability of eGFR values estimated with a creatinine measurement from a point of care (StatSensor®) compared with measured GFR (mGFR) by a gold standard method. Methods:We prospectively included 113 patients undergoing renal function assessment. We compared eGFR using creatinine from capillary blood or venous blood measured by StatSensor® and measured GFR (mGFR) by Passing Bablok regression. Performance of eGFR was estimated by biais, precision and accuracy. Results:A total of 113 subjects were included. Median eGFR values were 59 (10-132), 52 (10-123) and 51 (10-131) ml/min/1.73 m2 for enzymatic, capillary and venous measurements, respectively. There was no difference between P30 and P10 for the three eGFR values (p = 0.11 and p = 0.1 respectively). StatSensor® eGFR tended to be underestimated compared to mGFR. For CKD stage 4/5 patients, concordance was 79 and 84% for eGFR with capillary creatinine and venous creatinine respectively. For mGFR< 60 ml/min/1.73 m2, concordance was 84 and 88% with capillary creatinine and venous creatinine respectively. Conclusion:The use of a handheld blood creatinine monitoring system with eGFR calculation provides a good estimation of GFR and allow to identify patients at high risk of acute kidney injury.