Factors influencing young patient arrival date at the orthodontic office: a study of 456 cases / Facteurs influençant la date d'arrivée du jeune patient au cabinet d'orthodontie : une étude sur 456 cas.

Introduction: The arrival date young patient's first orthodontic consultation is unrestricted but may influence the choice of treatment plan as well as its modalities. The objective of this study was to determine the factors that influence the date of the first consultation at the orthodontic office: advice from a third party or a health professional, the patient's gender, the socioeconomic level, the actual need for orthodontic treatment, and the vertical and anteroposterior skeletal dysmorphia. Materials and Methods: Young patient's file younger than 16 years were systematically included. A Wilcoxon and Kruskal-Wallis test was performed in univariate and multivariate analysis. The threshold was 5%. Results: 456 young patients were included. Anteroposterior skeletal discrepancy, referral by an acquaintance, and socioeconomic level appeared to be factors influencing patient arrival date. Gender, actual need for orthodontic treatment, referral from a health professional, and vertical skeletal discrepancy did not influence the arrival date at the office. Discussion: The date of consultation is not related to the actual orthodontic treatment need. Word-of-mouth seems to play an important role. Patients seem to relate an anteroposterior discrepancy to the need to consult an orthodontist, but do not relate it to vertical discrepancy, although ventilation may be related to severe dysmorphia. Conclusion: This study encourages more communication about orthodontic treatment indications with patients and caregivers.

Introduction: La date d'arrivée du jeune patient en première consultation orthodontique est libre mais peut influencer le choix du plan de traitement, ainsi que ses modalités. L'objectif de cette étude était de déterminer les facteurs qui influencent la date de première consultation au cabinet d'orthodontie : le conseil d'un tiers ou d'un professionnel de santé, le genre du patient, le niveau socio-économique, le besoin réel de traitement orthodontique, la dysmorphie squelettique verticale et antéro-postérieure. Matériels et méthodes: Les dossiers de jeunes patients de moins de 16 ans ont été systématiquement inclus. Un test de Wilcoxon et Kruskal-Wallis a été effectué en analyse univariée et multivariée. Le seuil retenu était de 5 %. Résultats: Au total, 456 patients ont été inclus. Le décalage squelettique antéro-postérieur, le fait d'être adressé par une connaissance et le niveau socio-économique semblent être des facteurs influençant la date d'arrivée du jeune patient. Le genre, le besoin réel de traitement orthodontique, le fait d'être adressé par un professionnel de santé, le décalage squelettique vertical n'ont pas d'influence sur la date d'arrivée au cabinet. Discussion: La date de consultation n'est pas liée au besoin réel de traitement. Le bouche à oreille semble jouer un rôle important. Les patients semblent faire le lien entre un décalage antéro-postérieur et la nécessité de consulter un orthodontiste, mais ne le font pas pour le décalage vertical alors que la ventilation peut être liée à des dysmorphies sévères. Conclusion: Cette étude encourage à communiquer davantage sur les indications de traitement orthodontique avec les patients et les soignants.

Accurate height and length estimation in hospitalized children not fulfilling WHO criteria for standard measurement: a multicenter prospective study.

In hospitalized children, height should be measured. When world health organization (WHO) height measurement gold standards is impossible, the ideal height estimation technique is still unclear. We conducted an international prospective study in eight different pediatric intensive care units to assess the accuracy, precision, practicability, safety, and inter-rater reliability of 12 different height estimation techniques, based on body segment measurement extrapolation, or other calculations using previous or projected heights. All extrapolation techniques were performed on each child, and later compared to their WHO gold standard heights. A total of 476 patients were enrolled. In the < 2-year subgroup, board length use and growth chart extrapolation performed best. In the ≥ 2-year subgroup, growth chart extrapolation and parents' report were the most accurate, followed by height measurement alongside the body with a tape measure. In both groups, body segment extrapolations were poorly predictive and showed mean bias and limits of agreement that varied a lot with age. Most body segment-based techniques presented with frequent measurement difficulties, but children's safety was rarely compromised. The inter-rater reliability of body segment measurement was low in the < 2-year subgroup.Conclusions: To accurately estimate height in hospitalized children, health care professionals should integrate the accuracy, precision, practicability, and reliability of each measurement technique to select the most appropriate one. Body segment-based techniques were the least accurate and should probably not be used. Simple techniques like growth chart extrapolation, or measurement alongside the body (and length board measurement in the youngest) should be implemented in daily practice.Trial Registration: The study protocol was registered (12th April 2019) on the clinical-trial.gov website (NCT03913247).

Endovascular thrombectomy for acute ischaemic stroke with established large infarct (TENSION): 12-month outcomes of a multicentre, open-label, randomised trial.

BACKGROUND: Long-term data showing the benefits of endovascular thrombectomy for stroke with large infarct are scarce. The TENSION trial showed the safety and efficacy of endovascular thrombectomy in patients with ischaemic stroke and large infarct at 90 days. We aimed to investigate the safety and efficacy at 12 months of endovascular thrombectomy in patients who were enrolled in the TENSION trial. METHODS: TENSION was an open-label, blinded endpoint, randomised trial done at 40 hospitals across Europe and one hospital in Canada. We included patients (aged ≥18 years) with acute ischaemic stroke due to large vessel occlusion in the anterior circulation and who had a large infarct, as indicated by an Alberta Stroke Program Early Computed Tomographic Score (ASPECTS) of 3-5 on standard-of-care stroke imaging. We randomly assigned patients (1:1) to receive either endovascular thrombectomy with medical treatment or medical treatment only up to 12 h from stroke onset. The primary outcome was functional outcome across the entire range of the modified Rankin Scale at 90 days. Here, we report the prespecified 12-month follow-up analyses for functional outcome (using the simplified modified Rankin Scale questionnaire), quality of life (using the Patient-Reported Outcomes Measurement Information System 10-item [PROMIS-10] and EQ-5D questionnaires), post-stroke anxiety and depression (using the Patient Health Questionnaire-4 [PHQ-4]), and overall survival. Outcomes (except survival) were assessed in the intention-to-treat population; the survival analysis was based on treatment received. This trial is registered with ClinicalTrials.gov, NCT03094715, and is completed. FINDINGS: We enrolled patients between July 17, 2018, and Feb 21, 2023, when the trial was stopped early for efficacy. 253 patients were randomly assigned, 125 (49%) to endovascular thrombectomy and 128 (51%) to medical treatment only. Median follow-up was 8·36 months (IQR 0·02-12·00). Endovascular thrombectomy was associated with a shift in the distribution of scores on the modified Rankin Scale towards better functional outcome at 12 months (adjusted common odds ratio 2·39 [95% CI 1·47-3·90]). Endovascular thrombectomy was also associated with a better quality of life compared with medical treatment only, as reflected by median scores on the EQ-5D questionnaire index (0·7 [IQR 0·4-0·9] vs 0·4 [0·2-0·7]), median scores for health status on the EQ-5D questionnaire visual analogue scale (50 [IQR 35-70] vs 30 [5-60]), and median global physical health scores on the PROMIS-10 questionnaire (T-score 39·8 [IQR 37·4-50·8] vs 37·4 [32·4-44·9]); although there was not enough evidence to suggest a difference between groups in global mental health scores on PROMIS-10 (41·1 [IQR 36·3-48·3] vs 38·8 [31·3-44·7]) or the numbers of patients reporting anxiety (13 [22%] of 58 vs 15 [42%] of 36) and depression (18 [31%] vs 18 [50%]) on PHQ-4. Overall survival was slightly better in the endovascular thrombectomy group compared with medical treatment only (adjusted hazard ratio 0·70 [95% CI 0·50-0·99]). INTERPRETATION: In patients with acute ischaemic stroke from large vessel occlusion with established large infarct, compared with medical treatment only, endovascular thrombectomy was associated at 12 months after stroke with better functional outcome, quality of life, and overall survival. These findings suggest that the benefits of endovascular thrombectomy in patients with an ischaemic stroke and a large infarct are sustained in the long term and support the use of endovascular thrombectomy in these patients. FUNDING: European Union Horizon 2020 Research and Innovation Programme.

Value of green sign and chicken skin aspects for detecting malignancy of colorectal neoplasia in a prospective characterization study.

Background and study aims Accurate endoscopic characterization of colorectal lesions is essential for predicting histology but is difficult even for experts. Simple criteria could help endoscopists to detect and predict malignancy. The aim of this study was to evaluate the value of the green sign and chicken skin aspects in detection of malignant colorectal neoplasia. Patients and methods We prospectively characterized and evaluated the histology of all consecutive colorectal lesions detected during screening or referred for endoscopic resection (Pro-CONECCT study). We evaluated the diagnostic accuracy of the green sign and chicken skin aspects for detection of superficial and deep invasive lesions. Results 461 patients with 803 colorectal lesions were included. The green sign had a negative predictive value of 89.6% (95% confidence interval [CI] 87.1%-91.8%) and 98.1% (95% CI 96.7%-99.0%) for superficial and deep invasive lesions, respectively. In contrast to chicken skin, the green sign showed additional value for detection of both lesion types compared with the CONECCT classification and chicken skin (adjusted odds ratio [OR] for superficial lesions 5.9; 95% CI 3.4-10.2; P <0.001), adjusted OR for deep lesions 9.0; 95% CI 3.9-21.1; P <0.001). Conclusions The green sign may be associated with malignant colorectal neoplasia. Targeting these areas before precise analysis of the lesion could be a way of improving detection of focal malignancies and prediction of the most severe histology.

Real-World efficacy and safety of combination nivolumab plus ipilimumab for Untreated, Unresectable, pleural Mesothelioma: The Meso-Immune (GFPC 04-2021) trial.

BACKGROUND: First-line standard-of-care for unresectable, pleural mesothelioma (PM) changed with the phase 3 CheckMate 743 study results, showing that nivolumab plus ipilimumab (Nivo + Ipi) significantly extended overall survival (OS) versus platinum + pemetrexed chemotherapy for PM (median OS 18.1 versus 14.1 months; hazard ratio: 0.74; p = 0.002). Efficacy and safety data in real-world (rw) settings are needed to confirm these results. METHODS: This French multicenter, retrospective cohort study was undertaken to assess the outcomes of treatment-naïve PM patients given Nivo + Ipi via an early-access program (EAP). The primary objective was investigator-assessed real world -progression-free survival (PFS). The secondary objectives were the combination's -overall survival (OS) and safety. RESULTS: From 1 April 2021 to 15 Feb 2022, the analysis included 201 of the 305 EAP-enrolled patients treated in 63 centers (79.6 % men; median age: 75 years; 91.8 % Eastern Cooperative Oncology Group performance status (ECOG-PS) 0/1; 74.5 % epithelioid histology). With median (95 % CI) follow-up for all patients of 18.4 (17.7-19.2) months, -PFS and OS were 6.3 (5.3-7.5) and 18.9 (17.6-not reached (NR)) months, with 1-year OS at 66.4 % (60.1-73.3 %). Median OS and 1-year survival rates were 21.0 (18.7-NR) and 70.8 % (63.9 %-780.6 %), and 14.1 (10.9-21.0) months and 54.9 % (42.8 %-70.4 %) for epithelioid and non-epithelioid PM subgroups, respectively. PFS was equal between the two subgroups. Grade 3-4 adverse events occurred in 23.3 % of patients and three deaths were treatment-related. CONCLUSIONS: For this unselected PM population, efficacy and safety outcomes compared favorably with CheckMate 743 trial results.

Cost-effectiveness of endovascular thrombectomy for acute ischemic stroke with established large infarct in Germany: a decision tree and Markov model.

BACKGROUND: Recent studies, including the TENSION trial, support the use of endovascular thrombectomy (EVT) in acute ischemic stroke with large infarct (Alberta Stroke Program Early Computed Tomography Score (ASPECTS) 3-5). OBJECTIVE: To evaluate the cost-effectiveness of EVT compared with best medical care (BMC) alone in this population from a German healthcare payer perspective. METHODS: A short-term decision tree and a long-term Markov model (lifetime horizon) were used to compare healthcare costs and quality-adjusted life years (QALYs) between EVT and BMC. The effectiveness of EVT was reflected by the 90-day modified Rankin Scale (mRS) outcome from the TENSION trial. QALYs were based on published mRS-specific health utilities (EQ-5D-3L indices). Long-term healthcare costs were calculated based on insurance data. Costs (reported in 2022 euros) and QALYs were discounted by 3% annually. Cost-effectiveness was assessed using incremental cost-effectiveness ratios (ICERs). Deterministic and probabilistic sensitivity analyses were performed to account for parameter uncertainties. RESULTS: Compared with BMC, EVT yielded higher lifetime incremental costs (€24 257) and effects (1.41 QALYs), resulting in an ICER of €17 158/QALY. The results were robust to parameter variation in sensitivity analyses (eg, 95% probability of cost-effectiveness was achieved at a willingness to pay of >€22 000/QALY). Subgroup analyses indicated that EVT was cost-effective for all ASPECTS subgroups. CONCLUSIONS: EVT for acute ischemic stroke with established large infarct is likely to be cost-effective compared with BMC, assuming that an additional investment of €17 158/QALY is deemed acceptable by the healthcare payer.

Safety and Patient-Reported outcomes of atezolizumab plus chemotherapy with or without bevacizumab in stage IIIB/IV non-squamous non-small cell lung cancer with EGFR mutation, ALK rearrangement or ROS1 fusion progressing after targeted therapies (GFPC 06-2018 study).

BACKGROUND: In an open-label multicenter non-randomized non-comparative phase II study in patients with stage IIIB/IV non-squamous non-small cell lung cancer (NSCLC), oncogenic addiction (EGFR mutation or ALK/ROS1 fusion), with disease progression after tyrosine-kinase inhibitor and no prior chemotherapy (NCT04042558), atezolizumab, carboplatin, pemetrexed with or without bevacizumab showed some promising result. Beyond the clinical evaluation, we assessed safety and patient-reported outcomes (PROs) to provide additional information on the relative impact of adding atezolizumab to chemotherapy with and without bevacizumab in this population. MATERIALS: Patients received platinum-pemetrexed-atezolizumab-bevacizumab (PPAB cohort) or, if not eligible, platinum-pemetrexed-atezolizumab (PPA cohort). The incidence, nature, and severity of adverse events (AEs) were assessed. PROs were evaluated using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-Core 30 and EORTC QLQ-Lung Cancer 13). RESULT: Overall, 68 (PPAB) and 72 (PPA) patients were evaluable for safety. Grade 3-4 AEs occurred in 83.8% (PPAB) and 63.9% (PPA). Grade 3-4 atezolizumab-related AEs occurred in 29.4% and 19.4%, respectively. Grade 3-4 bevacizumab-related AEs occurred in 36.8% (PPAB). Most frequent grade 3-4 AEs were neutropenia (19.1% in PPAB; 23.6% in PPA) and asthenia (16.2% in PPAB; 9.7% in PPA). In PPAB, we observed a global stability in global health security (GHS) score, fatigue and dyspnea with a constant tendency of improvement, and a significant improvement in cough. In PPA, we observed a significant improvement in GHS score with a significant improvement in fatigue, dyspnea and cough. At week 54, we observed an improvement from baseline in GHS score for 49.2% of patients. In both cohorts, patients reported on average no clinically significant worsening in their overall health or physical functioning scores. CONCLUSION: PPAB and PPA combinations seem tolerable and manageable in patients with stage IIIB/IV non-squamous NSCLC with oncogenic addiction (EGFR mutation or ALK/ROS1 fusion) after targeted therapies.

Bioreactance assessment of cardiac output lacks reliability for the follow-up of patients with pulmonary hypertension.

Cardiac output (CO) is one of the primary prognostic factors evaluated during the follow-up of patients treated for pulmonary hypertension (PH). It is recommended that it be measured using the thermodilution technique during right heart catheterization. The difficulty to perform iterative invasive measurements on the same individual led us to consider a non-invasive option. The aims of the present study were to assess the agreement between CO values obtained using bioreactance (Starling™ SV) and thermodilution, and to evaluate the ability of the bioreactance monitor to detect patients whose CO decreased by more than 15% during follow-up and, accordingly, its usefulness for patient monitoring. A prospective cohort study evaluating the performance of the Starling™ SV monitor was conducted in patients with clinically stable PH. Sixty patients referred for hemodynamic assessment were included. CO was measured using both the thermodilution technique and bioreactance during two follow-up visits. A total of 60 PH patients were included. All datasets were available at the baseline visit (V0) and 50 of them were usable during the follow-up visit (V1). Median [IQR] CO was 4.20 l/min [3.60-4.70] when assessed by bioreactance, and 5.30 l/min [4.57-6.20] by thermodilution (p<0.001). The Spearman correlation coefficient was 0.51 [0.36-0.64], and the average deviation on Bland-Altman plot was -1.25 l/min (95% CI [-1.48-1.01], p<0.001). The ability of the monitor to detect a variation in CO of more than 15% between two follow-up measurements, when such variation existed using thermodilution, was insufficient for clinical practice (AUC = 0.54, 95% CI [0.33-0.75]).

Correlation between antifungal clinical practices and a new clinical decision support system ANTIFON-CLIC® for the treatment of invasive candidiasis: a retrospective multicentre study.

BACKGROUND: Invasive candidiasis is still recognized as a major cause of morbidity and mortality. To support clinicians in the optimal use of antifungals for the treatment of invasive candidiasis, a computerized decision support system (CDSS) was developed based on institutional guidelines. OBJECTIVES: To evaluate the correlation of this newly developed CDSS with clinical practices, we set-up a retrospective multicentre cohort study with the aim of providing the concordance rate between the CDSS recommendation and the medical prescription (NCT05656157). PATIENTS AND METHODS: Adult patients who received caspofungin or fluconazole for the treatment of an invasive candidiasis were included. The analysis of factors associated with concordance was performed using mixed logistic regression models with department as a random effect. RESULTS: From March to November 2022, 190 patients were included from three centres and eight departments: 70 patients from centre A, 84 from centre B and 36 from centre C. Overall, 100 patients received caspofungin and 90 received fluconazole, mostly (59%; 112/190) for empirical/pre-emptive treatment. The overall percentage of concordance between the CDSS and medical prescriptions was 91% (173/190) (confidence interval 95%: 82%-96%). No significant difference in concordance was observed considering the centres (P > 0.99), the department of inclusion (P = 0.968), the antifungal treatment (P = 0.656) or the indication of treatment (P = 0.997). In most cases of discordance (n = 13/17, 76%), the CDSS recommended fluconazole whereas caspofungin was prescribed. The clinical usability evaluated by five clinicians was satisfactory. CONCLUSIONS: Our results demonstrated the high correlation between current antifungal clinical practice and this user-friendly and institutional guidelines-based CDSS.

Feasibility of a screening and prevention procedure for risks associated with dysphagia in older patients in geriatric units: the DYSPHAGING pilot study protocol.

BACKGROUND: Dysphagia, particularly sarcopenic dysphagia, is frequent in frail older patients. Sarcopenic dysphagia is a swallowing disorder caused by sarcopenia, corresponding to a loss of muscle mass and strength. It frequently leads to inhalation and to the decrease of food intake, leading the patient to enter a vicious circle of chronic malnutrition and frailty. The awareness of the major health impacts of sarcopenic dysphagia is recent, explaining a low rate of screening in the population at risk. In this context, methods of prevention, evaluation and intervention of sarcopenic dysphagia adapted to the most at-risk population are necessary. METHODS: The DYSPHAGING (dysphagia & aging) pilot study is a prospective, multicentre, non-comparative study aiming to estimate the feasibility of an intervention on allied health professionals using the DYSPHAGING educational sheet designed to implement a two-step procedure 'screen-prevent' to mitigate swallowing disorders related to sarcopenic dysphagia. After obtaining oral consent, patients are screened using Eating Assessment Tool-10 Score. In case of a score≥2, procedures including positional manoeuvres during mealtimes, food and texture adaptation should be implemented. The primary endpoint of the study is the feasibility of this two-step procedure (screening-prevention measures) in the first 3 days after patient's consent.The study will include 102 patients, with an expected 10% rate of non-analysable patients. Participants will be recruited from acute geriatric wards, rehabilitation centres and long-term care units, with the hypothesis to reach a feasibility rate of 50% and reject a rate lower than 35%. ETHICS AND DISSEMINATION: The study protocol was approved according to French legislation (CPP Ile-de-France VII) on 15 February 2023. The results of the primary and secondary objectives will be published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT05734586.

Traction-assisted endoscopic submucosal dissection for resection of ileocecal valve neoplasia: a French retrospective multicenter case series.

BACKGROUND: The ileocecal valve (ICV) is considered to be one of the most difficult locations for endoscopic submucosal dissection (ESD). The objective of this study was to evaluate the efficacy and safety of traction-assisted ESD in this situation. METHODS: All patients who underwent traction-assisted ESD for an ICV lesion at three centers were identified from a prospective ESD database. En bloc and R0 rates were evaluated. Factors associated with non-R0 resection were explored. RESULTS: 106 patients with an ICV lesion were included. The median lesion size was 50 mm (interquartile range 38-60) and 58.5% (62/106) invaded the terminal ileum. The en bloc and R0 resection rates were 94.3% and 76.4%, respectively. Factors associated with non-R0 resection were lesions covering ≥75% of the ICV (odds ratio [OR] 0.21. 95%CI 0.06-0.76; P=0.02), and involving the anal lip (OR 0.36, 95%CI 0.13-0.99; P=0.04) or more than two sites on the ICV (OR 0.27, 95%CI 0.07-0.99; P=0.03). CONCLUSION: Traction-assisted ESD for treatment of ICV lesions was a safe and feasible option. Large lesions and anal lip involvement appeared to be factors predictive of difficulty.

Comprehensive Ophthalmological Evaluation in Atopic Dermatitis.

INTRODUCTION: Atopic dermatitis (AD), a chronic type 2 inflammatory skin disease, is frequently associated with ocular surface diseases (OSD) which may appear or worsen under anti-type 2-targeted treatments. However, the exact prevalence of OSD and the ophthalmology referral criteria remain ill-defined in AD patients before initiating such biotherapies. We aimed to characterize the prevalence, the nature and the factors related to OSD development in AD that may justify an ophthalmological management. METHODS: A total of 98 consecutive AD inpatients without biological treatment were retrospectively included. These were systematically evaluated by an ophthalmologist during their dermatological care. Clinical and laboratory data were analysed to characterize OSD and their risk factors. RESULTS: OSD were found in 83/98 AD patients (85%); mainly dry eye syndrome (64%, 63/98), allergic conjunctivitis (42%, 41/98), posterior (33%, 32/98), and anterior blepharitis (27%, 26/98). In AD patients without ocular symptoms, OSDs were also frequently found (63%, 12/19) and were mostly mild. Risk factors for OSD were history of allergic rhinitis, allergic sensitization, head and neck AD, ocular symptoms (foreign body sensation in the eye, burning, itching, photophobia), and total IgE level >3,000 kU/L. CONCLUSION: The prevalence of OSD was high, even in asymptomatic patients. The risk factors identified may indicate the need for ophthalmological examination for therapeutic management, especially when biological agents targeting type 2 inflammation are considered.

Systematic Resection of the Visible Scar After Incomplete Endoscopic Resection of Rectal Neuroendocrine Tumors.

INTRODUCTION: When initial resection of rectal neuroendocrine tumors (r-NETs) is not R0, persistence of local residue could lead to disease recurrence. This study aimed to evaluate the interest of systematic resection of non-R0 r-NET scars. METHODS: Retrospective analysis of all the consecutive endoscopic revisions and resections of the scar after non-R0 resections of r-NETs. RESULTS: A total of 100 patients were included. Salvage endoscopic procedure using endoscopic submucosal dissection or endoscopic full-thickness resection showed an R0 rate of near 100%. Residual r-NET was found in 43% of cases. DISCUSSION: In case of non-R0 resected r-NET, systematic scar resection by endoscopic full-thickness resection or endoscopic submucosal dissection seems necessary.

Cross-cultural adaptation of the CRS-PRO questionnaire into French.

BACKGROUND: Chronic rhinosinusitis (CRS), encompasses many different clinical patterns with variable response to treatment. Precise criteria specifying disease severity and control are lacking in the current literature. Our aim was to perform a cross-cultural adaptation of the CRS-PRO, creating a French version for use as a routine questionnaire in the assessment of patients with CRS. METHODS: The CRS-PRO questionnaire was translated according to the recommendations of the International Society for Pharmacoeconomics and Outcomes Research (ISPOR) through a three-step procedure including a backward translation. RESULTS: Seven of 12 items were initially discordant between the three translators before achieving consensus (Step 1). Two of 12 items were discordant between the backward translation and the initial CRS-PRO version regarding the word "mucus"(Step 2). Step 3 allowed the creation of a French proof-read version of the CRS-PRO questionnaire. Thirty patients were included for initial validation, mean age of 49.2 ± 15 years and 63.3% (19/30) male. It took them 67 ± 23 s to complete the questionnaire without any patients requiring more than 2 min. CONCLUSION: This study presents the French version of the CRS-PRO questionnaire-an adapted, validated, and well-accepted instrument to evaluate the CRS symptoms in the French speaking population.

The Need for Centralization for Small Intestinal Neuroendocrine Tumor Surgery: A Cohort Study from the GTE-Endocan-RENATEN Network, the CentralChirSINET Study.

BACKGROUND: The concept of surgical centralization is becoming more and more accepted for specific surgical procedures. OBJECTIVE: The aim of this study was to evaluate the relationship between procedure volume and the outcomes of surgical small intestine (SI) neuroendocrine tumor (NET) resections. METHODS: We conducted a retrospective national study that included patients who underwent SI-NET resection between 2019 and 2021. A high-volume center (hvC) was defined as a center that performed more than five SI-NET resections per year. The quality of the surgical resections was evaluated between hvCs and low-volume centers (lvCs) by comparing the number of resected lymph nodes (LNs) as the primary endpoint. RESULTS: A total of 157 patients underwent surgery in 33 centers: 90 patients in four hvCs and 67 patients in 29 lvCs. Laparotomy was more often performed in hvCs (85.6% vs. 59.7%; p < 0.001), as was right hemicolectomy (64.4% vs. 38.8%; p < 0.001), whereas limited ileocolic resection was performed in 18% of patients in lvCs versus none in hvCs. A bi-digital palpation of the entire SI length (95.6% vs. 34.3%, p < 0.001), a cholecystectomy (93.3% vs. 14.9%; p < 0.001), and a mesenteric mass resection (70% vs. 35.8%; p < 0.001) were more often performed in hvCs. The proportion of patients with ≥8 LNs resected was significantly higher (96.3% vs. 65.1%; p < 0.001) in hvCs compared with lvCs, as was the proportion of patients with ≥12 LNs resected (87.8% vs. 52.4%). Furthermore, the number of patients with multiple SI-NETs was higher in the hvC group compared with the lvC group (43.3% vs. 25.4%), as were the number of tumors in those patients (median of 7 vs. 2; p < 0.001). CONCLUSIONS: Optimal SI-NET resection was significantly more often performed in hvCs. Centralization of surgical care of SI-NETs is recommended.

Endovascular thrombectomy for acute ischaemic stroke with established large infarct: multicentre, open-label, randomised trial.

BACKGROUND: Recent evidence suggests a beneficial effect of endovascular thrombectomy in acute ischaemic stroke with large infarct; however, previous trials have relied on multimodal brain imaging, whereas non-contrast CT is mostly used in clinical practice. METHODS: In a prospective multicentre, open-label, randomised trial, patients with acute ischaemic stroke due to large vessel occlusion in the anterior circulation and a large established infarct indicated by an Alberta Stroke Program Early Computed Tomographic Score (ASPECTS) of 3-5 were randomly assigned using a central, web-based system (using a 1:1 ratio) to receive either endovascular thrombectomy with medical treatment or medical treatment (ie, standard of care) alone up to 12 h from stroke onset. The study was conducted in 40 hospitals in Europe and one site in Canada. The primary outcome was functional outcome across the entire range of the modified Rankin Scale at 90 days, assessed by investigators masked to treatment assignment. The primary analysis was done in the intention-to-treat population. Safety endpoints included mortality and rates of symptomatic intracranial haemorrhage and were analysed in the safety population, which included all patients based on the treatment they received. This trial is registered with ClinicalTrials.gov, NCT03094715. FINDINGS: From July 17, 2018, to Feb 21, 2023, 253 patients were randomly assigned, with 125 patients assigned to endovascular thrombectomy and 128 to medical treatment alone. The trial was stopped early for efficacy after the first pre-planned interim analysis. At 90 days, endovascular thrombectomy was associated with a shift in the distribution of scores on the modified Rankin Scale towards better outcome (adjusted common OR 2·58 [95% CI 1·60-4·15]; p=0·0001) and with lower mortality (hazard ratio 0·67 [95% CI 0·46-0·98]; p=0·038). Symptomatic intracranial haemorrhage occurred in seven (6%) patients with thrombectomy and in six (5%) with medical treatment alone. INTERPRETATION: Endovascular thrombectomy was associated with improved functional outcome and lower mortality in patients with acute ischaemic stroke from large vessel occlusion with established large infarct in a setting using non-contrast CT as the predominant imaging modality for patient selection. FUNDING: EU Horizon 2020.

Circulating H3K27 Methylated Nucleosome Plasma Concentration: Synergistic Information with Circulating Tumor DNA Molecular Profiling.

The molecular profiling of circulating tumor DNA (ctDNA) is a helpful tool not only in cancer treatment, but also in the early detection of relapse. However, the clinical interpretation of a ctDNA negative result remains challenging. The characterization of circulating nucleosomes (carrying cell-free DNA) and associated epigenetic modifications (playing a key role in the tumorigenesis of different cancers) may provide useful information for patient management, by supporting the contributive value of ctDNA molecular profiling. Significantly elevated concentrations of H3K27Me3 nucleosomes were found in plasmas at the diagnosis, and during the follow-up, of NSCLC patients, compared to healthy donors (p-value < 0.0001). By combining the H3K27Me3 level and the ctDNA molecular profile, we found that 25.5% of the patients had H3K27Me3 levels above the cut off, and no somatic alteration was detected at diagnosis. This strongly supports the presence of non-mutated ctDNA in the corresponding plasma. During the patient follow-up, a high H3K27Me3-nucleosome level was found in 15.1% of the sample, despite no somatic mutations being detected, allowing the identification of disease progression from 43.1% to 58.2% over molecular profiling alone. Measuring H3K27Me3-nucleosome levels in combination with ctDNA molecular profiling may improve confidence in the negative molecular result for cfDNA in lung cancer at diagnosis, and may also be a promising biomarker for molecular residual disease (MRD) monitoring, during and/or after treatment.

Surgery of primary lung carcinoid tumors at metastatic stage: A national study from the French Group of Endocrine Tumors (GTE) and ENDOCAN-RENATEN network.

The outcome following surgery for patients with primary lung neuroendocrine tumors at metastatic stage remains poorly characterized. We conducted a retrospective national study including patients with metastatic lung neuroendocrine tumors at diagnosis. We performed a safety study to evaluate major morbidity and mortality of surgical resection of the primary tumor and compared patients in the operative to the nonoperative group. A total of 155 patients were included: 41 in the operative group and 114 in the nonoperative group, median age was 64 years. Metastases were mainly located in the liver (74.2%) and the bone (49.7%). The primary endpoint was met as the rate of major complications was 4.9% and there was no postoperative mortality. In the operative group 42.5% of patients had improvement of their pulmonary symptoms versus 14.4% in the nonoperative group. The median overall survival was not reached in the operative group and was 4.3 years (95% CI [3.5;4.9]) in the nonoperative group (univariate analysis, HR = 0.42 95% CI [0.23-0.77], p = .002). After multivariate analysis, only an ECOG-PS ≥1 (vs. 0, HR = 2.44, 95% CI [1.46;4.07], p = .001) and >1 metastatic site (vs. 1; HR = 1.83, 95% CI [1.06;3.16], p = .030) remained significantly associated with overall survival. The resection of the primary tumor was not significantly associated with overall survival (HR = 0.63, 95% CI [0.32;1.24], p = .183). In conclusion, surgery of primary lung neuroendocrine tumors at metastatic stage is a safe option that should be considered in selected patients in order to improve symptoms with a view to improving their quality of life. Larger studies are warranted to evaluate the impact of surgery on survival.

Clustering of trajectories with mixed effects classification model: Inference taking into account classification uncertainties.

Classifying patient biomarker trajectories into groups has become frequent in clinical research. Mixed effects classification models can be used to model the heterogeneity of longitudinal data. The estimated parameters of typical trajectories and the partition can be provided by the classification version of the expectation maximization algorithm, named CEM. However, the variance of the parameter estimates obtained underestimates the true variance because classification uncertainties are not taken into account. This article takes into account these uncertainties by using the stochastic EM algorithm (SEM), a stochastic version of the CEM algorithm, after convergence of the CEM algorithm. The simulations showed correct coverage probabilities of the 95% confidence intervals (close to 95% except for scenarios with high bias in typical trajectories). The method was applied on a trial, called low-cyclo, that compared the effects of low vs standard cyclosporine A doses on creatinine levels after cardiac transplantation. It identified groups of patients for whom low-dose cyclosporine may be relevant, but with high uncertainty on the dose-effect estimate.